Zac1 (Lot1), a potential tumor suppressor gene, and the gene for e- sarcoglycan are maternally imprinted genes: Identification by a subtractive screen of novel uniparental fibroblast lines
Por:
Piras G., Kharroubi A.E., Kozlov S., Escalante-Alcalde D., Hernandez L., Copeland N.G., Gilbert D.J., Jenkins N.A., Stewart C.L.
Publicada:
1 ene 2000
Resumen:
Imprinted genes are expressed from one allele according to their parent of origin, and many are essential to mammalian embryogenesis. Here we show that the ?-sarcoglycan gene (Sgce) and Zac1 (Lot1) are both paternally expressed imprinted genes. They were identified in a subtractive screen for imprinted genes using a cDNA library made from novel parthenogenetic and wild-type fibroblast lines. Sgce is a component of the dystrophin-sarcoglycan complex, Zac1 is a nuclear protein inducing growth arrest and/or apoptosis, and Zac1 is a potential tumor suppressor gene. Sgce and Zac1 are expressed predominantly from their paternal alleles in all adult mouse tissues, except that Zac1 is biallelic in the liver and Sgce is weakly expressed from the maternal allele in the brain. Sgce and Zac1 are broadly expressed in embryos, with Zac1 being highly expressed in the liver primordium, the umbilical region, and the neural tube. Sgce, however, is strongly expressed in the allantoic region on day 9.5 but becomes more widely expressed throughout the embryo by day 11.5. Sgce is located at the proximal end of mouse chromosome 6 and is a candidate gene for embryonic lethality associated with uniparental maternal inheritance of this region. Zac1 maps to the proximal region of chromosome 0, identifying a new imprinted locus in the mouse, homologous with human chromosome 6q24-q25. In humans, unipaternal disomy for this region is associated with fetal growth retardation and transient neonatal diabetes mellitus. In addition, loss of expression of ZAC has been described for a number of breast and ovarian carcinomas, suggesting that ZAC is a potential tumor suppressor gene.
Filiaciones:
Piras G.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Life Technologies, Rockville, MD 20849, United States
Kharroubi A.E.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Kozlov S.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Escalante-Alcalde D.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Hernandez L.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Copeland N.G.:
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Gilbert D.J.:
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Jenkins N.A.:
Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Stewart C.L.:
Cancer and Devmtl. Biol. Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Res./Devmt. C., Frederick, MD 21702, United States
Lab. of Cancer and Devmtl. Biology, ABL-Basic Research Program, NCI-FCRDC, P.O. Box B, Frederick, MD 21702, United States
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