Irradiation prolongs survival of Alport mice.
Alport syndrome is a hereditary nephropathy that results in irreversible, progressive renal failure. Recent reports suggested that bone marrow transplantation (BMT) has a beneficial, short-term effect on renal injury in Alport (Col4a3(-/-)) mice, but its long-term effects, especially with regard to survival, are unknown. In this study, Alport mice received a transplant of either wild-type or Col4a3(-/-) bone marrow cells. Surprising, laboratory evaluations and renal histology demonstrated similar findings in both transplanted groups. Transplanted cells accounted for >10% of glomerular cells at 8 wk, but type IV collagen alpha3 chains were not detected in glomerular basement membranes of either group by immunofluorescence or Western blot analysis, although Col4a3 mRNA in the kidney could be amplified by reverse transcription-PCR in knockout mice that received a transplant of wild-type bone marrow. Both transplanted groups, however, survived approximately 1.5 times longer than untreated knockout mice (log rank P < 0.05). These data suggested that irradiation, which preceded BMT, may have conferred a survival benefit; therefore, the survival time of knockout mice was assessed after sublethal irradiation (3, 6, and 7 Gy) without subsequent BMT. A strong positive correlation between irradiation dosage and survival time was identified (P < 0.0001). In conclusion, the improved survival observed in Alport mice that received a transplant of wild-type bone marrow might be primarily attributed to as-yet-unidentified effects of irradiation.
Katayama
Kan
K
Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, 21-153 Noda, Tsu, Mie, 514-0826, Japan. a3huufbj@ztv.ne.jp
Kawano
Mitsuo
M
Naito
Ichiro
I
Ishikawa
Hitoshi
H
Sado
Yoshikazu
Y
Asakawa
Nagisa
N
Murata
Tomohiro
T
Oosugi
Kazuki
K
Kiyohara
Michiyo
M
Ishikawa
Eiji
E
Ito
Masaaki
M
Nomura
Shinsuke
S
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009394:Nephritis, Hereditary / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014916:Whole-Body Irradiation; D014998:Y Chromosome
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain