Accelerated tubular cell senescence in SMP30 knockout mice.
Accelerated tubular cell senescence in SMP30 knockout mice.
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DOI：
10.14670/hh-21.1151
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发表时间：
2006-11
影响因子：
2
通讯作者：
W. Yumura;T. Imasawa;S. Suganuma;A. Ishigami;S. Handa;S. Kubo;K. Joh;N. Maruyama
中科院分区：
文献类型：
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作者：
W. Yumura;T. Imasawa;S. Suganuma;A. Ishigami;S. Handa;S. Kubo;K. Joh;N. Maruyama
肾脏衰老加速但不剧烈的实验模型似乎有助于认识肾脏功能如何随着年龄的增长而恶化的机制。衰老标志蛋白30（SMP 30）主要表达于肝细胞和近端肾小管细胞，其表达随年龄增长而降低，且与性别无关。因此，我们建立了一个SMP 30缺陷型小鼠品系与C57 BL/6背景的基因打靶，以调查是否这种分子参与肾小管细胞衰老。对12月龄的雄性SMP 30敲除（SMP 30 Y/-）小鼠和雄性野生型（SMPY/+）小鼠（n=5）进行组织学检查。其肾小管上皮细胞显示脂褐素沉积和衰老相关β-半乳糖苷酶（SA-β-GAL）的存在。然而，没有肾小管细胞萎缩。在电子显微镜下，SMP 30-KO小鼠显示出明显增大的溶酶体，其中含有电子致密物质。这些都是衰老的明显标志。我们在12个月大的SMP 30-KO小鼠中认识到衰老标志的早期表现。因此，该模型代表了在基因操作后在肾脏中表现出加速有序衰老的小鼠品系的第一份报告。
An experimental model with accelerated but not drastic renal senescence seemed useful to recognize the mechanisms of how kidney function deteriorates with age. Senescence marker protein-30 (SMP30), whose expression decreased with age and was sex-independent, is mainly expressed in hepatocytes and proximal tubular cells. Therefore, we established a SMP30 deficient strain of mice with a C57BL/6 background by gene targeting to investigate whether this molecule is involved in renal tubular cell senescence. Male SMP30 knockout (SMP30Y/-) mice and male wild-type (SMPY/+) mice (n=5) aged 12 months were examined histologically. Their tubular epithelia showed the deposition of lipofuscin and the presence of senescence-associated beta-galactosidase (SA-beta-GAL). However, no tubular cells were atrophic. In electron microscopy, SMP30-KO mice showed markedly enlarged lysosomes containing an electron dense substance. These are convincing hallmarks of senescence. We recognized the early manifestation of senescence hallmarks in SMP30-KO mice at 12 months old. Thus, this model represents the first report of a mouse strain that manifests accelerated ordinal senescence in a kidney after gene manipulation.