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2016 ; 17
(1
): 69
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Mouse chromosome 2 harbors genetic determinants of resistance to podocyte injury
and renal tubulointerstitial fibrosis
#MMPMID27230548
Sasaki H
; Kimura J
; Nagasaki K
; Marusugi K
; Agui T
; Sasaki N
BMC Genet
2016[May]; 17
(1
): 69
PMID27230548
show ga
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.