Genetic background influences susceptibility to exencephaly in Scavenger receptor Class B type 1-deficient mouse embryos.

Introduction: Neural tube defects (NTD) are congenital malformations influenced by genetic and environmental factors. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1) exhibit female-skewed cranial NTD (exencephaly). This defect is preventable by maternal vitamin E supplementation in a C57BL/6J:129S1/SvImJ (B6:129) 1:1 background. In humans, genetic variability-such as differences across races or ethnic groups-modulates NTD penetrance and severity.

Aim and methods: This study compared reproductive outcomes and NTD incidence in two colonies of SR-B1-deficient mice (SR-B1 and SR-B1/J) with shared origin but differing backcrossing histories. The genetic background of each strain was determined using single-nucleotide-polymorphism (SNP)-based sequencing analysis.

Results: SR-B1/J mice showed significantly smaller litter sizes, slower development, and higher NTD incidence in SR-B1 KO embryos at gestational day 9.5 (E9.5) compared to SR-B1 mice. SNP analysis revealed a 50 % contribution of the 129 strain in SR-B1 mice versus 80 % in SR-B1/J mice. We also evaluated the preventive effect of maternal vitamin E supplementation in the SR-B1/J colony. Feeding dams a vitamin E-enriched diet reduced NTD incidence in the SR-B1/J colony, consistent with previous findings in the SR-B1 colony.

Discussion: This study highlights the critical influence of genetic background on NTD susceptibility in SR-B1 KO mice and demonstrates that vitamin E can reduce NTD risk across different genetic backgrounds. These findings underscore the importance of considering genetic variability in translational research and pave the way for further exploration of genetic modifiers that could enhance our understanding and prevention of NTD.