Sasaki Hayato, Marusugi Kiyoma, Kimura Junpei, Kitamura Hiroshi, Nagasaki Ken-ichi, Torigoe Daisuke, Agui Takashi, Sasaki Nobuya
Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University.
Biomed Res. 2015;36(5):323-30. doi: 10.2220/biomedres.36.323.
Tensin2 (Tns2) is thought to be a component of the cytoskeletal structures linking actin filaments with focal adhesions and is known to play a role as an intracellular signal transduction mediator through integrin in podocytes, although the mechanism by which it functions remains unclear. A Tns2-null mutation (nph) leads to massive albuminuria following podocyte foot process effacement in the ICGN mice, the origin of the mutation, and the DBA/2J (D2) mice, but not in the C57BL/6J (B6) mice or 129(+Ter)/SvJcl (129T) mice. Elucidating the reasons for these differences in diverse genetic backgrounds could help in unraveling Tns2 function in podocytes. We produced congenic mice in which Tns2(nph) was introgressed into a FVB/NJ background (FVB-Tns2(nph)), and evaluated the progression of kidney disease. FVB-Tns2(nph) mice developed albuminuria, renal fibrosis and renal anemia as seen in ICGN mice. The FVB-Tns2(nph) mice demonstrated podocyte foot process alteration under an electron microscope by as early as 4 weeks of age. This revealed that FVB strain is susceptible to Tns2-deficiency.
张力蛋白2（Tns2）被认为是将肌动蛋白丝与粘着斑连接起来的细胞骨架结构的一个组成部分，并且已知它在足细胞中通过整合素作为细胞内信号转导介质发挥作用，尽管其作用机制仍不清楚。Tns2基因敲除突变（nph）在ICGN小鼠、该突变的起源以及DBA/2J（D2）小鼠中导致足细胞足突消失后出现大量蛋白尿，但在C57BL/6J（B6）小鼠或129(+Ter)/SvJcl（129T）小鼠中则不会出现。阐明不同遗传背景下这些差异的原因有助于揭示Tns2在足细胞中的功能。我们培育了将Tns2(nph)导入FVB/NJ背景的同源基因小鼠（FVB-Tns2(nph)），并评估了肾脏疾病的进展。FVB-Tns2(nph)小鼠出现了蛋白尿、肾纤维化和肾性贫血，这与ICGN小鼠的情况相似。FVB-Tns2(nph)小鼠在电子显微镜下最早在4周龄时就表现出足细胞足突改变。这表明FVB品系对Tns2缺陷敏感。
