Interstrain differences in murine daunomycin-induced nephrosis.
Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism.
Kimura
M
M
Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Takahasi
H
H
Ohtake
T
T
Sato
T
T
Hishida
A
A
Nishimura
M
M
Honda
N
N
D000419:Albuminuria / Q000453:epidemiology; D000818:Animals; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003630:Daunorubicin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005805:Genes, MHC Class I / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006200:Hair Color / Q000235:genetics; D015994:Incidence; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008807:Mice, Inbred BALB C / Q000235:genetics; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D008811:Mice, Inbred DBA / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D005810:Multigene Family; D009393:Nephritis / Q000209:etiology* / Q000235:genetics* / Q000652:urine; D013045:Species Specificity
D003182:Complement C5; D004247:DNA; D003630:Daunorubicin