Skip to main content

Filter Search Results

Publication Year

Animal Models

Topic Area

Methods

Funding Mechanism

Division of Comparative Medicine

Collaborating ICs

Selected Grantee Publications

Impaired Skeletal Development by Disruption of Presenilin-1 in Pigs and Generation of Novel Pig Models for Alzheimer's Disease

Uh et al., Journal of Alzheimer's Disease. 2024.

https://pubmed.ncbi.nlm.nih.gov/39177593/

This study explored the effects of presenilin 1 (PSEN1) disruption on vertebral malformations in male and female PSEN1 mutant pigs. Researchers observed significant skeletal impairments and early deaths in pigs with a PSEN1 null mutation, mirroring phenotypes seen in mouse models of Alzheimer’s disease (AD). This porcine model provides valuable insights into pathological hallmarks of PSEN1 mutations in AD, offering a robust platform of therapeutic exploration. The findings establish pigs as an essential translational model for AD, enabling advanced studies on pathophysiology and treatment development for human skeletal and neurological conditions. Supported by ORIP (U42OD011140), NHLBI, NIA, NIAID.

DAZL Knockout Pigs as Recipients for Spermatogonial Stem Cell Transplantation

Lara et al., Cells. 2023.

https://pubmed.ncbi.nlm.nih.gov/37947660/

Spermatogonial stem cell (SSC) transplantation is a technique that holds potential for addressing male infertility, as well as generation of genetically modified animal models. DAZL (Deleted in Azoospermia–Like) is a conserved RNA-binding protein important for germ cell development, and DAZL knockout (KO) causes defects in germ cell commitment and differentiation. Investigators characterized DAZL-KO pigs as SSC transplantation recipients. DAZL-KO pigs support donor-derived spermatogenesis following SSC transplantation, but low spermatogenic efficiency currently limits their use for the production of offspring. Supported by ORIP (R01OD016575) and NIGMS.

Limited Expansion of Human Hepatocytes in FAH/RAG2-Deficient Swine

Nelson et al., Tissue Engineering – Part A. 2021.

https://pubmed.ncbi.nlm.nih.gov/34309416/

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. Nelson et al. engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 (RAG2) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. They identified the mechanism of the eventual graft rejection by the intact NK cell population. They confirmed the presence of residual adaptive immunity in this model of immunodeficiency. Supported by ORIP (U42OD011140).