title: Genetic background strongly influences the severity of glomerulosclerosis in mice.
abstract: The ICGN mouse strain is a glomerulosclerosis (GS) model that shows characteristic proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which are the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for GS in ICGN mice and found the deletion mutation of the tensin2 (Tns2) gene that creates both a premature stop codon and dramatically decreases mRNA expression levels within the region of the major QTL (this mutation was designated Tns2(nep)). The severity of GS varies considerably in humans and other animals, indicating the influence of several genes controlling the disease phenotype. In this study, to identify the modifier/resistant gene(s) for GS, we produced congenic strains carrying the Tns2(nep) mutation on the C57BL/6J (B6) genetic background and analyzed GS severity. Interestingly, the B6 congenic mice exhibited milder phenotypes than the ICGN strain mice. The results suggest that B6 mice have a modifier(s) of GS resistance. Therefore, identification of the modifier loci in B6 mice will provide important new information regarding gene interactions controlling GS.
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nagasaki
authors.forename: Zulkifli
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
mesh_terms: D000419:Albuminuria / Q000235:genetics; D000740:Anemia / Q000209:etiology / Q000235:genetics; D000818:Animals; D001806:Blood Urea Nitrogen; D003433:Crosses, Genetic; D017931:DNA Primers; D003928:Diabetic Nephropathies / Q000235:genetics*; D017353:Gene Deletion; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D040641:Quantitative Trait Loci; D012720:Severity of Illness Index; D000070876:Tensins
chemical_list: D017931:DNA Primers; D006454:Hemoglobins; D008840:Microfilament Proteins; D000070876:Tensins