Senescence marker protein-30 knockout mouse as a novel murine model of senile lung.
Senescence marker protein-30 (SMP30) was originally identified as a novel protein of which expression decreases in an androgen-independent manner with aging in the rat liver and functions to protect cells from apoptosis. By reverse transcription-polymerase chain reaction analysis, SMP30 mRNA transcripts were found in the mouse lung, liver, kidney, testis and cerebrum. We examined SMP30 expression in the mouse liver, kidney and lung during aging and a distinct temporal profile of SMP30 expression was found in each tissue; the SMP30 mRNA level peaked at 1-3 months of age and decreased thereafter in the liver (the highest at 1 month of age followed by a rapid decline and consistently low thereafter in the kidney), and peaked at 12 months of age in the lung. To investigate the physiological role of SMP30 in the lung, immunohistochemical studies of wild-type (SMP30Y/+) mice and histopathological examinations of SMP30 knockout (SMP30Y/-) mice were performed. Immunoreactivity against anti-SMP30 antibody was mainly detected in bronchial epithelial cells and strongly detected at 6-12 months of age. Morphometric analysis was performed to measure the mean linear intercept and destructive index, and found peripheral airspace enlargement without alveolar destruction in SMP30Y/- mice at 1, 3 and 6 months of age compared with the SMP30Y/+ mice. Our results strongly suggest that SMP30Y/- mice could be a novel model for a senile lung and further examinations of SMP30Y/- mice may offer clues to elucidate the mechanisms of the development of pulmonary diseases in the elderly.
Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Takanori
T
Mori
Akihito
A
Ishigami
Kuniaki
K
Seyama
Reiko
R
Onai
Sachiho
S
Kubo
Kazue
K
Shimizu
Naoki
N
Maruyama
Yoshinosuke
Y
Fukuchi
D000375:Aging; D000818:Animals; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015238:Sulfotransferases
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C513324:Rgn protein, mouse; D015238:Sulfotransferases; C028152:alcohol sulfotransferase