title: Mouse chromosome 2 harbors genetic determinants of resistance to podocyte injury and renal tubulointerstitial fibrosis.
abstract: Tensin2 deficiency results in alterations in podocytes and subsequent glomerular and tubulointerstitial injuries. However, this pathology is critically dependent on genetic background. While the Tensin2-deficient podocytes of resistant murine strains, including C57BL/6J mice, remain almost intact, susceptible murine strains with Tensin2 deficency, including ICGN mice, develop chronic kidney disease following alterations in the podocyte foot processes. In a previous study, genome-wide linkage analysis was utilized to identify the quantitative trait loci associated with the disease phenotypes on mouse chromosome 2. This study investigated the disease phenotypes of chromosome 2 consomic and subcongenic strains.
  
  
  
  ICGN consomic mice introgressed with chromosome 2 from the C57BL/6J mouse were generated and found to exhibit milder renal failure than that in ICGN mice. We developed 6 subcongenic strains that carry C57BL/6J-derived chromosomal segments from the consomic strain. One showed significantly milder albuminuria, another showed significantly milder tubulointerstitial injury, and the both showed significantly milder glomerular injury.
  
  
  
  These data indicate that mouse chromosome 2 harbors two major genes associated with the severities of nephropathy induced by Tensin2 deficiency. The proximal region on chromosome 2 contributes to the resistance to tubulointerstitial fibrosis. In contrast, the distal region on chromosome 2 contributes to the resistance to podocyte injury. This study would be helpful to discover the biological mechanism underlying the renal injury, and may lead to the identification of therapeutic targets.
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada, 034-8628, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Bunkyo 2-3, Chitose, 066-0052, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nagasaki
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada, 034-8628, Japan.
authors.forename: Kiyoma
authors.initials: K
authors.lastname: Marusugi
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Faculty of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada, 034-8628, Japan. nobsasa@vmas.kitasato-u.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D005355:Fibrosis; D056426:Genetic Loci / Q000235:genetics; D006720:Homozygote; D007684:Kidney Tubules / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000473:pathology*; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology
keywords: Albuminuria; Chronic kidney disease; Renal fibrosis; Tensin2