Selected Grantee Publications
Systematic Ocular Phenotyping of 8,707 Knockout Mouse Lines Identifies Genes Associated With Abnormal Corneal Phenotypes
Vo et al., BMC Genomics. 2025.
https://pubmed.ncbi.nlm.nih.gov/39833678
Corneal dysmorphologies (CDs) are a group of acquired but predominantly genetically inherited eye disorders that cause progressive vision loss and can be associated with systemic abnormalities. This study aimed to identify candidate CD genes in humans by looking at knockout mice with targeted deletions of orthologous genes that exhibited statistically significant corneal abnormalities. Analysis of data from 8,707 knockout mouse lines identified 213 candidate CD genes; 176 (83%) genes have not been implicated previously in CD. Bioinformatic analyses implicated candidate genes in several signaling pathways (e.g., integrin signaling pathway, cytoskeletal regulation by Rho GTPase, FAS signaling pathway), which are potential therapeutic targets. Supported by ORIP (U42OD011175, R03OD032622, UM1OD023221), NEI, and NHGRI.
Spatiotemporal Characterization of Cyclooxygenase Pathway Enzymes During Vertebrate Embryonic Development
Leathers et al., Developmental Biology. 2025.
https://pubmed.ncbi.nlm.nih.gov/39581452/
The cyclooxygenase (COX) pathway plays a fundamental role in embryonic development. Disruptions of the COX pathway during pregnancy cause developmental anomalies, including craniofacial clefts, impaired gut innervation, and neural tube defects in the embryo. Researchers used Gallus gallus embryos to study the expression of COX pathway enzymes during neurulation. COX-1 protein expression was upregulated in cells undergoing mitosis, whereas COX-2 protein expression was ubiquitous. This study provides spatiotemporal expression data of COX pathway enzymes at key embryonic development stages in G. gallus and guides future studies focused on defining the role of these enzymes during embryonic development. Supported by ORIP (T35OD010956), NEI, NIDCR, and NIGMS.
The Widely Used Ucp1-Cre Transgene Elicits Complex Developmental and Metabolic Phenotypes
Halurkar et al., Nature Communications. 2025.
https://pubmed.ncbi.nlm.nih.gov/39824816
Bacterial artificial chromosome technology is instrumental to mouse transgenics, including in studies of highly thermogenic brown adipose tissue and energy-storing white adipose tissue. Researchers discovered that male and female Ucp1-CreEvdr transgenic mice, which are commonly used to study fat tissue, may have unintended effects on metabolism and development. Findings revealed that these mice show changes in both brown and white fat function and disruptions in gene activity, suggesting broader physiological impacts than previously thought. This study emphasizes the need for careful validation of genetic tools in research to ensure accurate results, highlighting the potential concerns in using the Ucp1-CreEvdr model in metabolic and developmental studies. Supported by ORIP (R21OD034470, R21OD031907) NCATS, NIDCR, and NIDDK.