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Hybrid Rat Diversity Program

Grant Number: R24OD024617


Research Emphasis/ObjectivesHXb/BXH Recombinant inbred panel (30 strains), Divergent classic inbred strains (35 strains), FXLE/LEXF Recombinant inbred strains (34 strains)

The Hybrid Rat Diversity Program (HRDP) is a panel of genetically and phenotypically diverse inbred rat strains consisting of two panels of recombinant inbred strains and a group of classic inbred strains. The overall goal of this program is to establish this panel of 96 strains as a foundation for powerful complex trait mapping, correlation analysis, and transcription network analysis. The 96-strain HRDP panel includes the HXB/BXH recombinant inbred panel from the Czech Republic and the LEXF/FXLE recombinant inbred panel from Japan, as well as 33 classic inbred strains. These diverse but stable genetic strains provide the platform for reproducible experiments in both males and females to test the effects of genetic background or environmental conditions, as well as systems genetics. The HRDP program is establishing the panel of rats through rederivation; performing whole-genome sequencing; characterizing the strains and biobanking tissues; and distributing rats, tissues, and data to the scientific community.

Services Provided

The Hybrid Rat Diversity Program provides live rats, embryos, tissues, phenotypic data, and genomic data to investigators. The HRDP currently maintains living colonies of the strains rederived as part of the HRDP program. Investigators can request rats using the Medical College of Wisconsin Rat Request form (mcw.edu/-/media/MCW/Departments/Genomic-Sciences-and-Precision-Medicine-Center/externalratrequest.pdf?la=en). Investigators interested in tissues should contact ratrequest@mcw.edu. Genomic and phenotypic data for each of the 96 strains included in the HRDP can be accessed through the HRDP Portal at the Rat Genome Database (rgd.mcw.edu/wg/hrdp_panel/).

Contact Information

Hybrid Rat Diversity Program (Melinda Dwinell)
8701 Watertown Plank Road
Milwaukee, WI 53226
rgd.mcw.edu/wg/hrdp_panel/

Principal Investigator

Melinda Dwinell, Ph.D.
Phone: 414-955-4498
Fax: 414-955-6516
mrdwinel@mcw.edu

Other/Resource Contacts

Rat Requests (Including Tissues)
Phone: 414-955-4066
Fax: 414-955-6516
ratrequest@mcw.edu

Special Mouse Strain Resource

Grant Number: P40OD011102


Research Emphasis/Objectives

Many aspects of human health and disease are genetically complex; that is, they arise from multiple interactions between genetic, developmental, and environmental factors. Understanding this complexity is the basis of personalized medicine. Unfortunately, human genetic studies are still limited in a number of ways. These include inadequate, retrospective medical records; formidable sample size requirements; insufficient statistical power to study genetic interactions; and insufficient mechanistic information about many genes. These obstacles are easily addressed using nonhuman mammalian models, such as mice, that are designed for fine-scale dissection of genetic complexity (i.e., systems genetics). For these reasons, the biomedical research community has invested in the development genetically diverse inbred strains and genetic reference populations of mice as tools for systems genetics research.

The Special Mouse Strain Resource (SMSR) at The Jackson Laboratory serves as the biorepository for these unique sets of strains, ensuring permanent and open access from high health status, quality controlled, state-of-the-art facilities. The resource currently consists of more than 300 strains, including the widely used BXD and Collaborative Cross strain panels, but importantly, the strains available in the SMSR are changed and developed as dictated by the needs of research community.

The major activities of the SMSR are to (1) archive, maintain, and distribute these strains to qualified biomedical researchers, (2) provide complete, accurate, and accessible information related to the mouse resources, (3) confer with an external advisory board of thought leaders from the complex trait community to define current and future resources, and (4) provide leadership in best practices for research and reproducibility using SMSR resources.

The SMSR also provides infrastructure, outreach, and collaborative opportunities for the development of new tools for complex trait analysis, as well as access to existing strains and populations for large-scale multicenter projects. It also conducts research to expand tools for genetic engineering of specialized mapping strains.

Current Research

The CC/DO and BXD platforms harness the natural inbred strain variation that is needed for systems genetics studies. The nine-founder inbred strains (A/J, 129S1/SvImJ, NZO/HILtJ, NOD/LtJ, CAST/EiJ, WSB/EiJ, PWK/EiJ, C57BL/6J, and DBA/2J [BXD]) from which this natural variation is derived are often used at the outset of a systems genetics study to establish heritability, a process that requires a survey of inter- to intrastrain variance in quantitative phenotypic trait(s). These genetically diverse inbred strains are also frequently used for validation studies of variants that underlie QTL. In both types of studies, genetic engineering is often required to achieve the goals of a given experiment. These manipulations include introduction of disease driver alleles, cell/tissue-specific fluorescent reporters, epitope-tagged proteins, conditional alleles, and other engineered molecular "tools," as well as simple allele swaps. Unfortunately, "tool strains" that carry commonly needed genetic manipulations are not currently available for genetically diverse inbred strains such as CC/DO, BXD, or the founder inbred strains used to create these RI panels. To address this gap, the SMSR program will create a series of commonly used tool strains across genetically diverse backgrounds.

Services Provided

The SMSR offers the following services in concert with The Jackson Laboratory: (1) breeding and rederivation services, including dedicated supply, speed expansion, congenic development, strain rescue, and microinjection; (2) cryopreservation, storage, and recovery services, including sperm and embryo cryopreservation; (3) phenotyping and pathology services; and (4) genome sciences services, including gene mapping, genome scanning, and QTL analysis.

Contact Information

JAX SMSR
The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609
Special Mouse Strain Resource

Principal Investigators

Laura Reinholdt, Ph.D.
Phone: 207-288-6693
laura.reinholdt@jax.org

Cat Lutz, Ph.D.
Phone: 207-288-6341
cat.lutz@jax.org

Rat Resource and Research Center

Grant Number: P40OD011062


Research Emphasis/Objectives

The Rat Resource and Research Center (RRRC) provides the biomedical community with ready access to valuable rat strains/stocks, embryonic stem cells, and other related services that enhance the use of rats in research and shift the burden for maintaining and distributing rat models from individual investigators to a centralized repository where high standards of genetic quality control and health monitoring can be maintained to maximize research reproducibility.

Current Research

Research efforts are focused on improving cryopreservation and in vitro fertilization in the rat, generating new rat models needed by the research community, and characterizing the gut microbiota of rat models to better understand its impact on model phenotypes.

Services Provided

Animals

The RRRC imports high-quality, well-characterized rat strains and stocks from donating investigators using an online application process and active recruitment of valuable models. High-demand strains are rederived to a pathogen-free state and distributed as live animals. Low-demand strains are cryopreserved as germplasm and are cryorecovered upon request. All strains/stocks imported and exported from the RRRC are subjected to rigorous genetic analysis and health monitoring. The RRRC is an approved vendor for many institutions.

Biological Materials

Germline competent rat embryonic stem cell lines, including several on different genetic backgrounds and several containing EGFP, are available. Germplasm (embryos and/or spermatozoa) and genomic DNA are available from rat strains/stocks. Tissue or organ samples from specific strains can be collected, preserved, and/or fixed to the investigator’s specifications.

Fee-for-Service

A number of services are available on a fee-for-service basis. The RRRC encourages research collaborations with investigators and can provide consultation on colony management, husbandry, reproductive biology, gamete and embryo cryopreservation, genetics, model generation, and characterization, including phenotyping, histopathology, and behavioral testing.

Cryopreservation and Cryostorage

Cryopreservation and cryostorage of sperm and embryos is performed routinely for the strains/stocks donated to the RRRC, and these services are available to investigators for non-RRRC strains as insurance against loss of valuable models or to generate banks of frozen material for use to refresh foundation colonies to minimize genetic drift.

Rederivation and Cryo-Resuscitation

Embryo transfer or intracytoplasmic sperm injection (ICSI) can be used to resuscitate and rederive strains/stocks. Investigators receive recovered litters with confirmed genetics and a pathogen-free health status.

Colony Management and Breeding Services

The RRRC can maintain small colonies of rats for investigators who may not have the expertise or facility space to do so. Other services include moving genetic mutations to new genetic backgrounds using a speed congenic approach, timed matings and embryo collection.

Genetic Testing

Services available for both RRRC and non-RRRC rats include, but are not limited to, genotyping (standard PCR, PCR followed by restriction endonuclease digest or nucleotide sequence analysis, RT-PCR, qPCR, and probe-based allelic discrimination), sex determination assays, genotyping assay development, validation/optimization of genotyping assays, single nucleotide polymorphism (SNP) analysis, speed congenic assay development, fluorescent in situ hybridization, and karyotyping.

Microinjection Services

The RRRC can perform microinjection of zygotes to produce transgenic rats or genetically modified rats using CRISPR/Cas9 genome-editing technologies.

Generation of Rat Models

In partnership with the MU Animal Modeling Core (research.missouri.edu/animal-modeling), the RRRC can assist with the design and generation of transgenic rats, create knock-out and knock-in rats using CRISPR/Cas9 technology, and genetically manipulate rat embryonic stem cells to make chimeric animals.

Embryonic Stem Cell Lines

The RRRC can assist with the isolation and characterization, including testing for germline competency, of new embryonic stem cells from rat strains of interest.

Pathology

Available services include, but are not limited to, pathogen detection through a collaborating diagnostic laboratory (IDEXX BioResearch), gross necropsy examination, tissue collection, and histopathologic evaluation of tissues.

Microbiota Analysis

Services available for RRRC and non-RRRC rats include, but are not limited to, targeted 16S rRNA microbiome characterization and analysis, consultation on the impact of differing microbiota on model phenotype and reproducibility, manipulation of microbiomes through rederivation or fecal transplants, and collaborative studies assessing the impact of microbiome on model phenotypes.

Training

The RRRC is affiliated with the University of Missouri (MU) Comparative Medicine Program (cmp.missouri.edu), a training program for veterinarians pursuing careers in biomedical research. Externships for veterinary students and post-D.V.M. trainees are available through the MU Comparative Medicine Program.

Contact Information

Rat Resource and Research Center
Room S118
4011 Discovery Drive
Columbia, MO 65201
rrrc.us

Principal Investigator

Elizabeth Bryda, Ph.D.
Phone: 573-882-5504
Fax: 573-882-9857
brydae@missouri.edu

Resource/Additional Resource Contact

RRRC Customer Service
Phone: 888-673-3444 or 573-884-6076
rrrc@missouri.edu

Reproductive Services

Yuksel Agca, D.V.M., Ph.D.
agcay@missouri.edu

Health Monitoring and Pathology

Craig Franklin, D.V.M., Ph.D.
franklinc@missouri.edu

Metagenomics

Aaron Ericsson, D.V.M., Ph.D.
ericssona@missouri.edu

Informatics, Coordination and Service Center for the Mutant Mouse Resource & Research Centers

Grant Number: U42OD010983


Research Emphasis/Objectives

The Informatics, Coordination and Service Center (ICSC) is located at the University of California, Davis, and serves as the centralized support center for the MMRRC (Mutant Mouse Resource & Research Centers) consortium. 

Services Provided

The ICSC is responsible for providing bioinformatics, website functionality and maintenance, strain acquisition, coordination and curation, and customer service to support the MMRRC Centers.

Contact Information

MMRRC-ICSC
c/o Mouse Biology Program
University of California, Davis
2795 Second Street, Suite 400
Davis, CA 95618
mmrrc.org

Principal Investigator

Ian Korf, Ph.D.
Phone: 530-757-5710
Fax: 530-757-3284
service@mmrrc.org

Strain Acquisition Coordinator

sacoord-comment@mmrrc.org

Customer Service

Phone: 800-910-2291 (North America) or 530-757-5710 (International)
Fax: (530) 757-3284
service@mmrrc.org

Mutant Mouse Resource & Research Center at The Jackson Laboratory

Grant Number: U42OD010921


Research Emphasis/Objectives

For most of the last century, mutant mice have contributed greatly to our basic understanding of the genetics underlying mammalian biology and human disease. The scientific community’s demand for well-characterized, genetically stable, phenotypically reproducible, high-health-status mutant mice remains significant and poised to grow due to widespread adoption of genome-editing technologies. Comprised of four regional distribution centers, the primary responsibility of the Mutant Mouse Resource & Research Centers (MMRRC) is to facilitate a wide spectrum of research activities by serving as a reliable, readily accessible, quality-assured repository of mutant mouse strains. The MMRRC at The Jackson Laboratory (MMRRC-JAX) rapidly meets the needs of researchers through expedient order fulfillment, ready access to live mice for widely utilized mutant lines, and cryopreserved products. All activities are accomplished in concert with fellow consortium members and the Informatics, Coordination, and Service Center (ICSC). Founded in 1920, JAX brings nearly 100 years of repository experience, large-scale capacities for strain archiving and distribution, and research excellence in mammalian genetics and genomics to accomplish the following objectives:

  1. Identify, evaluate, and acquire biomedically significant, genetically-engineered, mutant mice for inclusion in the MMRRC program.
  2. Import/acquire and archive mouse strains into a high-quality, secure storage facility using state-of-the-art rederivation methods to eliminate specific pathogens and advanced cryopreservation techniques to safely store germplasm and embryos.
  3. Distribute mouse strains in the form of live mice, cryopreserved germplasm, or embryos, in addition to cryopreserved embyonic stem cell lines.
  4. Operate a state-of-the-art quality control program to ensure genetic stability by monitoring mutant genotype, mutant phenotype, and genetic background and to protect animal health by monitoring material tracking, pathogen testing, and standard operating procedures (SOPs).
  5. Develop awareness of the MMRRC by promoting mouse strains and research services, as well as provide outstanding customer service and technical support to the research community.
  6. Enhance the existing resources through model generation. 

Current Research

Systems genetics endeavors to explain the integration, coordination, and expression of genetic information across phenotypes at all scales (molecular, cellular, physiological, and population) and across many contexts (health, disease, infection, environment, etc.). These systems-level approaches operate on networks and have the potential to explain higher-order functions and emergent properties of biological systems. With the explosion of -omics technologies, advanced computational methods for big data analysis, and the availability of advanced genetic reference sequences for human and model organism populations, systems genetics approaches are more powerful than ever. Our research project is a pilot that will will generate the methodologies, capabilities, infrastructure, and proof-of-concept for an in vitro systems genetics service platform. This project is responsive to the rising interest in the integration of genetic diversity in biomedical research, a key growth area for the MMRRC consortium.

Services Provided

MMRRC-JAX offers the following services in concert with JAX:

  • Breeding and rederivation services, including dedicated supply, speed expansion, congenic development, strain rescue, and microinjection.
  • Cryopreservation, storage, and recovery services, including sperm and embryo cryopreservation.
  • Phenotyping and pathology services.
  • Genome sciences services, including gene mapping, genome scanning, and QTL analysis.

Contact Information

MMRRC-JAX
The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609-1500
https://www.jax.org/research-and-faculty/resources/mutant-mouse-resource-research-center 
mmrrc.org

Principal Investigators

Cathleen Lutz, Ph.D.
Phone: 207-288-6341
Fax: 207-288-6149
cat.lutz@jax.org

Laura Reinholdt, Ph.D. (Co-PI)
Phone: 207-288-6693
Fax: 207-288-6149
laura.reinholdt@jax.org

Resource/Additional Contact

Steve Rockwood
Phone: 207-288-6437
Fax: 207-288-6149
steve.rockwood@jax.org

Mutant Mouse Resource & Research Center at UNC-Chapel Hill

Grant Number: U42OD010924


Research Emphasis/Objectives

The research emphasis/objectives of the Mutant Mouse Research & Resource Center at The University of North Carolina at Chapel Hill (MMRRC-UNC) are the following:

  • Provide the mouse community access to updated computational tools to facilitate mouse genomics research.
  • Improve and standardize genome background analysis and reporting.
  • Develop a speed congenic analysis pipeline as the basis for a potential new service for the mouse genomics community.
  • Identify genomic regions in the mature sperm epigenome that differ by diet treatment and can be used as biomarkers to detect and reduce diet-induced variability in the MMRRC repository.
  • Measure the impact of changing from donor institution diet to MMRRC diet on sperm quality and epigenetics status.
  • Identify microbes required for colitis phenotype in collaborative cross strain.
  • Evaluate and validate the causative and functional role of identified hybrid microbiota and/or consortia in the pathogenesis of spontaneous colitis.

Services Provided

  1. Import, archive, distribute genetically engineered mouse strains, embryonic stem cell lines, and mouse embryonic fibroblast lines.
  2. Systems genetics for predictive mouse biology platforms, pipelines, and tools.
  3. Ensure quality control (genotype and genomic quality, health status, microbiome analysis).
  4. Consultation.
  5. Research and partnerships.
  6. Broad mouse services available from the UNC mouse program: collaborative cross, Gnotobiotic Rodent Resource, behavioral genetics, regenerative medicine, whole-animal imaging, high-throughput sequencing and informatics, systems immunogenetics, Mouse Phase I Unit, Animal Models Core, translational science.

Contact Information

MMRRC-UNC
CB#7519
Chapel Hill, NC 27599-7519
med.unc.edu/mmrrc

Principal Investigator

Terry Magnuson
Phone: 919-962-1319
Fax: 919-962-1476
tmagnuson@unc.edu

Mutant Mouse Resource & Research Center at UC Davis

Grant Number: U42OD012210


Research Emphasis/Objectives

The Mutant Mouse Resource & Research Center (MMRRC) at the University of California, Davis (UC Davis), was established in 1997 and is one of the founding institutions of the MMRRC national program.

With a growing archive of more than 50,000 mutant alleles, the MMRRC at UC Davis imports, archives, maintains, and distributes live mice, frozen germplasm, stem cells, and molecular vectors for use in biomedical research. The MMRRC accepts transgenics, knockouts, genome-edited, spontaneous, and other types kinds of mutant mouse lines at no cost to the donor. After quality control checks, rederivation, and cryopreservation, the MMRRC distributes pathogen-free breeding stock, germplasm, cells, and/or tissues to requesting investigators for a small fee. The MMRRC operates within the UC Davis Mouse Biology Program (MBP), a center of scientific excellence in mouse biology, genetic manipulation, and comprehensive phenotyping of mouse models of human disease.

Services Provided

Specialized Services: Fee-For-Service

The MMRRC at UC Davis provides a wide array of specialized services on a recharge basis. These services include custom model generation (e.g., homologous recombination in embyonic stem [ES] cells, Cre/LoxP, CRISPR/Cas9, etc.), assistive reproductive technologies (IVF, intracytoplasmic sperm injection [ICSI]), genotyping and genetic analysis, behavioral testing, gamete and embryo cryopreservation, construct design, gnotobiotics, phenotyping and analytics, imaging, advanced surgical models, and vivarium and colony management.

Animals

The MMRRC at UC Davis is committed to upholding the highest standards of experimental design and quality control that optimize reproducibility and rigor through the distribution of well-characterized inbred, hybrid, and mutant mice. This commitment involves the rederivation of mice from well-annotated and documented backgrounds to a pathogen-free status, allowing investigators to generate robust and reliable results.

Bioinformatics

The MMRRC at UC Davis offers investigators such informatics services as data collection, hosting, visualization, analysis, dynamic web presentation, and publication quality reporting.

Biological Materials

The MMRRC at UC Davis provides cryopreserved germplasm, genomic DNA, and tissue samples from mutant models.

Colony Management and Breeding Services

The MMRRC at UC Davis offers Speed Cohort Delivery (SCD) for rapidly generating and expanding mutant cohorts, transferring genetic mutations onto different genetic backgrounds, and managing breeding colonies of mice.

Cryopreservation and Cryostorage

A cryopreserved archive (embryos, sperm, and/or ES cells) is created and maintained for all mouse lines deposited into the MMRRC at UC Davis. The MMRRC provides cryopreservation services to investigators as protection against loss of valuable research models due to disease breakouts, genetic drift, or breeding interruptions. 

Cryo-Resuscitation and Rederivation

The MMRRC at UC Davis provides cryorecovery services to re-establish live mouse colonies from archived germplasm, including the use of IVF or ICSI and embryo transfer and Caesarian section. Investigators receive recovered litters with confirmed genetics, pathogen-free health status, and microbiome analysis.

Genetic Testing

The MMRRC at UC Davis offers a wide array of genetic testing services for mice, germplasm and cells, including endpoint generic and gene-specific genotyping, genetic fingerprinting and single nucleotide polymorphism (SNP) analysis, genomic integration analysis by target locus amplification, whole-exome and whole-genome sequencing, and more.

Genetic Engineering: ES Cell and Microinjection Services

The MBP utilizes a variety of different techniques, including genome editing (CRISPR/Cas9), transgenic insertion, and homologous recombination in ES cells, to generate constitutive, conditional, and inducible knockouts and knockins. We also offer Fast-Trak Genome Editing, which is on-demand de novo generation of specific alleles (indels to targeted insertions, patient variants, etc.) in mice using CRISPR/Cas9 genome editing. When requesting this service, researchers will be given prioritized attention at subsidized cost if they commit to depositing their newly generated mice into the MMRRC.

Imaging Services

The MMRRC at UC Davis offers non-invasive in vivo imaging and image analysis, including optical projection tomography (OPT), computerized tomography (CT), nuclear magnetic resonance (NMR), and PET/MRI, which allows for longitudinal in vivo imaging.

Gnotobiotic Research Services

The MMRRC at UC Davis offers exploration of the pathobiological integration of the microbiome in health and disease in a germ-free environment through its gnotobiotic mouse resource center (GMRC). Services include targeted microbiome characterization and analysis, consultation on the impact of differing microbiota on biology and disease in mice, studies assessing microbiome on model phenotypes, and the manipulation of microbiomes through rederivation and fecal transplants.

Phenotyping and Analytics

The MMRRC at UC Davis offers a full suite of observational and procedural testing platforms, including morphology, ataxia, gait, behavior, cardiology, brain response, body composition, exercise, and after-life services that include necropsy, gross anatomic pathology, tissue collection and processing, histopathology, and special staining.

Teaching Resources and Training

The MMRRC at UC Davis, in collaboration with the UC Davis Mouse Biology Program, offers training opportunities for undergraduates, graduate students, veterinary and medical students, and post-D.V.M. trainees.

Contact Information

Mutant Mouse Resource & Research Center
c/o Mouse Biology Program
University of California, Davis
2795 Second Street, Suite 400
Davis, CA 95618
mmrrc.ucdavis.edu

Principal Investigator

K. C. Kent Lloyd, D.V.M., Ph.D
Phone: 530-754-MMRRC (6677)
Fax: 530-757-3277
mmrrc@ucdavis.edu

Other/Resource Contacts

Renee Araiza
MMRRC Repository Manager
Phone: 530-757-3273
Fax: 530-757-3284
rsaraiza@ucdavis.edu

Customer Service

MMRRC at UC Davis
Phone: 530-754-MMRRC (6677) or 530-757-8476
Fax: 530-757-3284
mmrrc@ucdavis.edu

Mutant Mouse Resource & Research Centers


Consortium OverviewMMRRC logo

The Mutant Mouse Resource & Research Centers (MMRRC) is NIH’s premier national mouse repository that consists of four Centers (University of California, Davis; University of Missouri; University of North Carolina at Chapel Hill; and The Jackson Laboratory) and one Informatics, Coordination and Service Center (ICSC). The Centers provide the worldwide biomedical research community with access to more than 50,000 strains of mutant mice and embyonic stem cells. With one of the largest nonprofit repositories of mouse models in the world, the MMRRC distributes and archives models to advance the biomedical research efforts of the scientific research community. Each month through partnerships with researchers around the world, the MMRRC enhances critical research with a continuously expanding catalog of mouse models of human disease. To learn more about the individual MMRRC Centers or how to donate a mouse model, please visit the links below.

MMRRC Portal 
mmrrc.org

Strain Submission 
mmrrc.org/submission/submIntro.php

Catalog Search 
mmrrc.org/catalog/StrainCatalogSearchForm.php

Donate a Mouse Model 
mmrrc.org/submission/strain_submission_terms.php

Customer Service
Phone: 800-910-2291 (North America) or 530-757-5710 (International)
Fax: 530-757-3284
service@mmrrc.org

Mutant Mouse Resource & Research Center at the University of Missouri

Grant Number: U42OD010918


Center OverviewMissouri University IDEXX Discovery Ridge

The Mutant Mouse Resource & Research Center (MMRRC) at the University of Missouri (MU-MMRRC) was established in 2000. The MU-MMRRC is a consortium of investigators that includes Craig Franklin, D.V.M., Ph.D. (Co-PI), Jim Amos-Landgraf, Ph.D. (Co-PI), Elizabeth Bryda, Ph.D., Yuksel Agca, D.V.M., Ph.D., and Aaron Ericsson, D.V.M., Ph.D. at the University of Missouri.

Research Emphasis/Objectives

Research efforts focus on assessing the role of complex gut microbiota in model phenotypes, reproducibility, and translatability by developing well-controlled antigen-experienced microbiota, economic strategies by which complex microbiota can be transferred, and tools to better sample microbiota kinetics. These studies have yielded new paradigms by which the MMRRC can now provide mice harboring one or more standardized complex microbiota and aid investigators wishing to assess the role of microbiota in their model phenotypes. 

Services Provided

Animals

The overall goal is to distribute high-quality, well-characterized genetically-engineered (i.e., transgenic, knockout) or spontaneous mutant mice to investigators. To this end, the MMRRC selects and imports mouse strains and stocks important to the biomedical research community, rederives mice to a pathogen-free state, cryopreserves gametes and embryos, performs genotyping and infectious disease monitoring to ensure the quality of the mice, and distributes live mice to investigators.

Biological Materials

In addition to live animals, cryopreserved germplasm, genomic DNA, or tissue samples from models can be provided.

Fee-for-Service

A number of services are available on a fee-for-service basis. The MMRRC encourages research collaborations with investigators and can provide consultation on colony management, husbandry, reproductive biology, gamete and embryo cryopreservation, genetics, and model generation and characterization (including phenotyping, histopathology, behavioral testing, and metagenomics).

Cryopreservation and Cryostorage

Cryopreservation and cryostorage of sperm and embryos are performed routinely for the strains/stocks donated to the MMRRC, and these services are available to investigators for non-MMRRC strains as insurance against loss of valuable models or to generate banks of frozen material for use to refresh foundation colonies to minimize genetic drift.

Rederivation and Cryo-Resuscitation

Either in vitro fertilization or intracytoplasmic sperm injection (ICSI) and subsequent embryo transfer techniques can be used to resuscitate and rederive strains/stocks. Investigators receive recovered litters with confirmed genetics and a pathogen-free health status.

Colony Management and Breeding Services

The MMRRC can maintain small colonies of mice for investigators who may not have the expertise or facility space to do so. Other services include moving genetic mutations to new genetic backgrounds using a speed congenic approach, timed matings, and embryo collection.

Genetic Testing

Services available for both MMRRC and non-MMRRC mice include but are not limited to genotyping (standard PCR, digital droplet PCR, PCR followed by restriction endonuclease digest or nucleotide sequence analysis, RT-PCR, qPCR, and probe-based allelic discrimination), sex determination assays, genotyping assay development, validation/optimization of genotyping assays, single nucleotide polymorphism (SNP) analysis, speed congenic assay development, fluorescent in situ hybridization, and karyotyping.

Embryonic Stem Cell and Microinjection Services

Services available for MMRRC mice and non-MMRRC mice include but are not limited to electroporation and selection in embyonic stem (ES) cells, genome editing (e.g., CRISPR/Cas9), and transgene development (e.g., plasmid, BAC).

Rodent Health Monitoring and Pathology

Services available for MMRRC mice and non-MMRRC mice include but are not limited to pathogen detection through a collaborating diagnostic laboratory (IDEXX BioAnalytics), gross necropsy examination, tissue collection, and histopathologic evaluation of tissues.

Metagenomics

Through a partnership with the University of Missouri Metagenomics Center, services available for MMRRC mice and non-MMRRC mice include but are not limited to targeted 16S rRNA or whole-genome microbiome characterization and analysis, consultation on the impact of differing microbiota on model phenotype and reproducibility and translatability, manipulation of microbiomes through rederivation or alternative procedures, and collaborative studies assessing the impact of microbiome on model phenotypes.

Animal Model Development

The MMRRC partners with the University of Missouri Animal Modeling Core (AMC) to create genetically engineered mice using contemporary state-of-the-art technologies. Services of the AMC include construct design, zygote injection or ES cell targeting, CRISPR/Cas9-mediated genome editing, genotyping assay development, and maintenance of animal colonies.

Training

MU-MMRRC is affiliated with the Comparative Medicine Program, a training program for veterinarians pursuing careers in biomedical research. Externships for veterinary students and post-D.V.M. trainees are available through the MU Comparative Medicine Program.

Contact Information

University of Missouri MMRRC
4011 Discovery Drive
Columbia, MO 65201
https://mu-mmrrc.com/ 

Principal Investigators

Craig Franklin, D.V.M., Ph.D., DACLAM, Co-PI
Phone: 573-882-6623
franklinc@missouri.edu

Jim Amos-Landgraf, Ph.D., Co-PI
Phone: 573-882-1514
amoslandgrafj@missouri.edu

Resource/Additional Contact

MMRRC Customer Service
Phone: 888-673-3444 or 573-884-6076
Fax: 573-882-9857
mmrrc@missouri.edu

Reproductive Services

Yuksel Agca, D.V.M., Ph.D.
agcay@missouri.edu

Genetics and Genotyping

Elizabeth Bryda, Ph.D.
Director, Rat Resource and Research Center
Director, MU Animal Modeling Core
brydae@missouri.edu

Metagenomics

Aaron Ericsson, D.V.M., Ph.D.
Director, MU Metagenomics Center
ericssona@missouri.edu

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