Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type Tsc2 gene.
We recently reported that a germ-line insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to dominantly inherited cancer in the Eker rat model. In this study, we constructed transgenic Eker rats with introduction of a wild-type Tsc2 gene to ascertain whether suppression of the Eker phenotype is possible. Rescue from embryonic lethality of mutant homozygotes (Eker/Eker) and suppression of N-ethyl-N-nitrosourea-induced renal carcinogenesis in heterozygotes (Eker/+) were both observed, defining the germ-line Tsc2 mutation in the Eker rat as embryonal lethal and tumor predisposing mutation. To the best of our knowledge, this is the first report of rescue from a naturally occurring dominantly inherited cancer. This transgenic rescue system will be useful to analyze Tsc2 gene function, its relation to tumorigenesis in vivo, and genetic-environmental interactions in carcinogenesis.
Kobayashi
T
T
Department of Experimental Pathology, Cancer Institute, Toshima-ku, Tokyo, Japan.
Mitani
H
H
Takahashi
R
R
Hirabayashi
M
M
Ueda
M
M
Tamura
H
H
Hino
O
O
D000818:Animals; D030801:Animals, Genetically Modified; D002277:Carcinoma / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D018095:Germ-Line Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009374:Neoplasms, Experimental / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins