Title

Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model.

Document Type

Article

Publication Date

8-2021

Publication Title

Journal of the American Society of Nephrology : JASN

Keywords

JMG

JAX Source

J Am Soc Nephrol 2021 Aug; 32(8):1961-1973

Volume

32

Issue

8

First Page

1961

Last Page

1973

ISSN

1533-3450

PMID

34045313

DOI

https://doi.org/10.1681/asn.2020060777

Grant

Alport Syndrome Foundation Grant

Abstract

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.

Comments

We acknowledge the contribution of Heidi Munger and the Genome Technologies Service at The Jackson Laboratory for expert assistance with RNAseq.

Please contact the Joan Staats Library for information regarding this document.

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