Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome.
Transgenic mouse strains carrying proviruses were generated by exposing mouse embryos to a recombinant retrovirus. Animals carrying a single provirus were intercrossed to derive mice homozygous for a given proviral insertion. Adult mice homozygous for the Mpv17 integration developed nephrotic syndrome and chronic renal failure. Histologically, affected kidneys showed progressive glomerular sclerosis. Similar lesions are seen in patients with progressive renal function deterioration. A probe to DNA sequences flanking the provirus detected a 1.7 kb RNA ubiquitously expressed during embryogenesis and in adults with high levels in kidney, brain, and heart. This RNA was not detected in tissues of homozygous animals, suggesting that the provirus interferes with RNA expression. Sequence analysis of the cDNA revealed that the gene encodes a 176 amino acid peptide containing hydrophobic regions, suggesting membrane association of the putative protein. The Mpv17 mutant is a potentially useful experimental system for studying mechanisms leading to renal disorders in man.
Whitehead Institute, Massachusetts Institute of Technology, Cambridge 02142.
H
H
Weiher
T
T
Noda
D A
DA
Gray
A H
AH
Sharpe
R
R
Jaenisch
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D009404:Nephrotic Syndrome / Q000235:genetics* / Q000473:pathology; D015345:Oligonucleotide Probes; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D015183:Restriction Mapping; D012190:Retroviridae / Q000235:genetics
D004251:DNA Transposable Elements; D008565:Membrane Proteins; C065292:Mpv17 protein, mouse; D015345:Oligonucleotide Probes; D011506:Proteins; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D004247:DNA