Accelerated tubular cell senescence in SMP30 knockout mice
W. Yumura1,2, T. Imasawa3, S. Suganuma2, A. Ishigami1, S. Handa1, S. Kubo1, K. Joh3 and N. Maruyama1
1Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 2Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, 3Department of Internal Medicine and Division of Immunopathology, Clinical Research Center, Chiba-East National Hospital, Chiba, Japan.
Offprint requests to: M.D. Ph.D. Toshiyuki Imasawa, Department of Internal Medicine and Division of Immunopathology, Clinical Research Center, Chiba-East National Hospital, 673 Nitona, Chuoh, Chiba, 260-8712, Japan. e-mail: email@example.com
Summary. 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 ß-galactosidase (SA-ß-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. Histol Histopathol 21, 1151-1156 (2006)
Key words: Renal senescence, Tubular cells, SMP30, Knockout mouse, Lipofuscin, Senescence-associated, ß-galactoside