title: Accelerated tubular cell senescence in SMP30 knockout mice.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Yumura
authors.forename: T
authors.initials: T
authors.lastname: Imasawa
authors.forename: S
authors.initials: S
authors.lastname: Suganuma
authors.forename: A
authors.initials: A
authors.lastname: Ishigami
authors.forename: S
authors.initials: S
authors.lastname: Handa
authors.forename: S
authors.initials: S
authors.lastname: Kubo
authors.forename: K
authors.initials: K
authors.lastname: Joh
authors.forename: N
authors.initials: N
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D016922:Cellular Senescence; D004848:Epithelium / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007684:Kidney Tubules / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D015238:Sulfotransferases; D013997:Time Factors
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008062:Lipofuscin; C513324:Rgn protein, mouse; D015238:Sulfotransferases; C028152:alcohol sulfotransferase