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Genetic backgrounds and modifier genes of NTD mouse models: An opportunity for greater understanding of the multifactorial etiology of neural tube defects

Lookup NU author(s): Parmveer Singh


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Neurulation, the early embryonic process of forming the presumptive brain and spinal cord, is highly complex and involves hundreds of genes in multiple genetic pathways. Mice have long served as a genetic model for studying human neurulation, and the resulting neural tube defects (NTDs) that arise when neurulation is disrupted. Because mice appear to show mostly single gene inheritance for NTDs and humans show multifactorial inheritance, mice sometimes have been characterized as a simpler model for the identification and study of NTD genes. But are they a simple model? When viewed on different genetic backgrounds, many genes show significant variation in the penetrance and expressivity of NTD phenotypes, suggesting the presence of modifier loci that interact with the target gene to affect the phenotypic expression. Looking at mutations on different genetic backgrounds provides us with an opportunity to explore these complex genetic interactions, which are likely to better emulate similar processes in human neurulation. Here, we review NTD genes known to show strain-specific phenotypic variation. We focus particularly on the gene Cecr2, which is studied using both a hypomorphic and a presumptive null mutation on two different backgrounds: one susceptible (BALB/c) and one resistant (FVB/N) to NTDs. This strain difference has led to a search for genetic modifiers within a region on murine chromosome 19. Understanding how genetic variants alter the phenotypic outcome in NTD mouse models will help to direct future studies in humans, particularly now that more genome wide sequencing approaches are being used.

Publication metadata

Author(s): Leduc RY, Singh P, McDermid HE

Publication type: Article

Publication status: Published

Journal: Birth Defects Research

Year: 2017

Volume: 109

Pages: 140-152

Online publication date: 21/10/2016

Acceptance date: 26/06/2016

ISSN (print): 2472-1727

Publisher: Wiley Periodicals, Inc.


DOI: 10.1002/bdra.23554

PubMed id: 27768235


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