Senescence marker protein-30 knockout mouse as an aging model.
A mouse strain lacking SMP30 can be regarded as a strain showing ultimate decrease of the SMP30 molecule. After three months of age, SMP30-KO mice had an increased mortality rate, compared with the SMP30-WT mice, all of which remained alive. Electron microscopic observation of the hepatocytes from 12-month-old SMP30-KO mice revealed many empty vacuoles, presumably lipid droplets, abnormally enlarged mitochondria with indistinct cristae, and exceptionally large lysosomes filled with electron-dense bodies. The total hepatic triglyceride concentration of SMP30-KO mice was approximately 3.6-fold higher than that of the age-matched wild type. Similarly, the total hepatic cholesterol of SMP30-KO mice reached an approximate 3.3-fold greater value than that of the comparative group. Total hepatic phospholipids of SMP30-KO mice achieved an approximately 3.7-fold higher level compared with that of the wild-type mice. The cells from SMP30-KO mice were sensitive to apoptotic reagents. Those results supported the idea that SMP30 has an antiapoptotic function with wide spectrum. These findings indicate that SMP30-KO mice are highly susceptible to various harmful reagents. This strain might be a useful tool for aging and biological monitoring.
Maruyama
Naoki
N
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan. maruyama@center.tmig.or.jp
Ishigami
Akihito
A
Kuramoto
Masashi
M
Handa
Setsuko
S
Kubo
Sachiho
S
Imasawa
Toshiyuki
T
Seyama
Kuniaki
K
Shimosawa
Tatsuo
T
Kasahara
Yasushi
Y
D000375:Aging; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D004583:Electrons; D022781:Hepatocytes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008954:Models, Biological; D018384:Oxidative Stress; D015238:Sulfotransferases; D013997:Time Factors
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; D002784:Cholesterol; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D002118:Calcium