Abstract
BackgroundTensin2 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.ResultsICGN 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0378-1) contains supplementary material, which is available to authorized users.
Highlights
Tensin2 deficiency results in alterations in podocytes and subsequent glomerular and tubulointerstitial injuries
Verification of Chronic kidney disease (CKD)-resistant loci on chromosome 2 For verification of the existence of the CKD-resistant loci on Chr 2 from the B6 mice, which are linked to all tested parameters for CKD, we produced ICGN consomic mice homozygously introgressed with Chr 2 (D2Mit1-D2Mit229, 2.23–88.99 cM) from the B6 mouse (ICGN-Chr 2B6) using marker-assisted backcrossing
There was no significant difference in blood urea nitrogen (BUN) between the ICGN and ICGN-Chr 2B6 mice, with no ICGN-Chr 2B6 mice and only a few ICGN mice showing an abnormal BUN level (Fig. 1a)
Summary
Tensin deficiency results in alterations in podocytes and subsequent glomerular and tubulointerstitial injuries. This pathology is critically dependent on genetic background. CKD is strongly linked to important diseases such as diabetes, hypertension and cardiovascular disease [2]. Faced with these outcomes, clinical research efforts over the last few decades have focused on preventing or delaying the Taking into account both renal structure and its role in the continuous filtration of blood flow, we can imagine that renal glomerular damage due to abnormal blood pressure or components is a potential risk factor for CKD progression. Podocyte injury is a common determining factor for progression toward many types of kidney
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