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Molecular and Cellular Biology, May 2000, p. 3308-3315, Vol. 20, No. 9
0270-7306/00/$04.00+0

Zac1 (Lot1), a Potential Tumor Suppressor Gene, and the Gene for epsilon -Sarcoglycan Are Maternally Imprinted Genes: Identification by a Subtractive Screen of Novel Uniparental Fibroblast Lines

Graziella Piras,1,dagger Aboubaker El Kharroubi,1 Serguei Kozlov,1 Diana Escalante-Alcalde,1 Lidia Hernandez,1 Neal G. Copeland,2 Debra J. Gilbert,2 Nancy A. Jenkins,2 and Colin L. Stewart1,*

Cancer and Developmental Biology Laboratory1 and Mammalian Genetics Laboratory,2 ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

Received 14 December 1999/Returned for modification 25 January 2000/Accepted 2 February 2000

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 varepsilon -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 10, 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.

* Corresponding author. Mailing address: Laboratory of Cancer and Developmental Biology, ABL-Basic Research Program, NCI-FCRDC, P.O. Box B, Frederick, MD 21702. Phone: (301) 846-1755. Fax: (301) 846-7117. E-mail: stewartc{at}mail.ncifcrf.gov.

dagger Present address: Life Technologies, Rockville, MD 20849.

Molecular and Cellular Biology, May 2000, p. 3308-3315, Vol. 20, No. 9
0270-7306/00/$04.00+0


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