Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model.
Journal of the American Society of Nephrology : JASN
J Am Soc Nephrol 2021 Aug; 32(8):1961-1973
Alport Syndrome Foundation Grant
BACKGROUND: Mutations in
METHODS: We created a cohort of genetically diverse XLAS male and female mice using the Diversity Outbred mouse resource and measured albuminuria, GFR, and gene expression. Using a quantitative trait locus approach, we mapped modifier genes that can best explain the underlying phenotypic variation measured in our diverse population.
RESULTS: Genetic analysis identified several loci associated with the variation in albuminuria and GFR, including a locus on the X chromosome associated with X inactivation and a locus on chromosome 2 containing
CONCLUSION: With this novel approach, we emulated the variability in the severity of kidney phenotypes found in human patients with Alport Syndrome through albuminuria and GFR measurements. This approach can identify modifier genes in kidney disease that can be used as novel therapeutic targets.
Takemon, Yuka; Wright, Valerie; Davenport, Bernard; Gatti, Daniel M.; Sheehan, Susan; Letson, Kelsey; Savage, Holly S; Lennon, Rachel; and Korstanje, Ron, "Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model." (2021). Faculty Research 2021. 153.