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129基因背景影响张力蛋白2缺陷小鼠对肾小球硬化的易感性。

The 129 genetic background affects susceptibility to glomerulosclerosis in tensin2-deficient mice.

作者信息

Nishino Tomohiro, Sasaki Nobuya, Nagasaki Ken-Ichi, Ichii Osamu, Kon Yasuhiro, Agui Takashi

机构信息

Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818.

出版信息

Biomed Res. 2012 Feb;33(1):53-6. doi: 10.2220/biomedres.33.53.

DOI:10.2220/biomedres.33.53
PMID:22361887
Abstract

The ICGN mouse strain is a glomerulosclerosis (GS) model that shows significant proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which represent the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we demonstrated that GS in ICGN mice can be attributed to the deletion mutation of the tensin2 (Tns2) gene (Tns2(nep)). Further, the C57BL/6J (B6) mouse is resistant to GS caused by this mutation. 129/Sv is also a popular strain; however, its susceptibility to GS has not been defined. Thus, to determine whether 129/Sv is resistant or susceptible to GS, we produced a congenic strain carrying Tns2(nep) on the 129(+Ter)/Sv (129T) background. 129T congenic mice (129T-Tns2(nep)) did not exhibit albuminuria, renal anemia, increases in BUN, or any severe pathological changes until at least 16 weeks of age. These results indicate that 129T is resistant to GS. Although their usage in biomedical studies is already widespread, 129/Sv mice may afford a late-onset and unique strain applicable to kidney disease research.

摘要

ICGN小鼠品系是一种肾小球硬化(GS)模型,表现出显著的蛋白尿、足细胞形态异常以及肾小球细胞外基质积累增加,这些代表了与导致终末期肾衰竭的多种肾脏疾病相关的最终共同病理特征。此前,我们证明ICGN小鼠的GS可归因于张力蛋白2(Tns2)基因的缺失突变(Tns2(nep))。此外,C57BL/6J(B6)小鼠对由该突变引起的GS具有抗性。129/Sv也是一种常用品系;然而,其对GS的易感性尚未明确。因此,为了确定129/Sv对GS是抗性还是易感,我们培育了一种在129(+Ter)/Sv(129T)背景上携带Tns2(nep)的近交系。129T近交系小鼠(129T-Tns2(nep))在至少16周龄之前未表现出蛋白尿、肾性贫血、血尿素氮升高或任何严重的病理变化。这些结果表明129T对GS具有抗性。尽管129/Sv小鼠在生物医学研究中的应用已经很广泛,但它们可能是一种适用于肾脏疾病研究的迟发性且独特的品系。

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引用本文的文献

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Life (Basel). 2023 May 24;13(6):1244. doi: 10.3390/life13061244.
2
Tensin 2-deficient nephropathy: mechanosensitive nephropathy, genetic susceptibility.Tensin 2 缺陷性肾病:机械敏感性肾病,遗传易感性。
Exp Anim. 2022 Aug 5;71(3):252-263. doi: 10.1538/expanim.22-0031. Epub 2022 Apr 19.
3
Deletion of the Tensin2 SH2-PTB domain, but not the loss of its PTPase activity, induces podocyte injury in FVB/N mouse strain.Tensin2 SH2-PTB 结构域缺失而非其 PTPase 活性丧失可诱导 FVB/N 鼠种足细胞损伤。
Exp Anim. 2020 Apr 24;69(2):135-143. doi: 10.1538/expanim.19-0101. Epub 2019 Nov 12.
4
Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.六个肾病基因的突变勾勒出一条可治疗的致病途径。
Nat Commun. 2018 May 17;9(1):1960. doi: 10.1038/s41467-018-04193-w.
5
Genetic loci for resistance to podocyte injury caused by the tensin2 gene deficiency in mice.导致小鼠肌腱蛋白 2 基因缺陷引起的足细胞损伤的抗性的遗传位点。
BMC Genet. 2018 Apr 10;19(1):24. doi: 10.1186/s12863-018-0611-1.
6
C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.C1-Ten 是一种 Nephrin 的 PTPase,通过激活 mTORC1 调节足细胞肥大。
Sci Rep. 2017 Sep 27;7(1):12346. doi: 10.1038/s41598-017-12382-8.
7
Mouse chromosome 2 harbors genetic determinants of resistance to podocyte injury and renal tubulointerstitial fibrosis.小鼠2号染色体含有对足细胞损伤和肾小管间质纤维化的抗性遗传决定因素。
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Tensin2-deficient mice on FVB/N background develop severe glomerular disease.FVB/N背景下的张力蛋白2缺陷小鼠会发生严重的肾小球疾病。
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