Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model.
Albuminuria
/ etiology
Animals
Chromosome Mapping
Collagen Type IV
/ genetics
Creatinine
/ urine
Disease Models, Animal
Female
Formins
/ genetics
Gene Expression
Glomerular Filtration Rate
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Mutation
Nephritis, Hereditary
/ complications
Phenotype
Podocytes
/ pathology
Proof of Concept Study
Quantitative Trait Loci
RNA-Seq
Sex Factors
Whole Genome Sequencing
Alport-s syndrome
albuminuria
gene expression
genetics and development
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
03
06
2020
accepted:
27
03
2021
pubmed:
29
5
2021
medline:
21
10
2021
entrez:
28
5
2021
Statut:
ppublish
Résumé
Mutations in 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. 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 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.
Sections du résumé
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.
Identifiants
pubmed: 34045313
pii: 00001751-202108000-00018
doi: 10.1681/ASN.2020060777
pmc: PMC8455275
doi:
Substances chimiques
Col4a5 protein, mouse
0
Collagen Type IV
0
Formins
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1961-1973Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202860/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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