title: Integration of a c-myc transgene results in disruption of the mouse Gtf2ird1 gene, the homologue of the human GTF2IRD1 gene hemizygously deleted in Williams-Beuren syndrome.
abstract: Transgenic mice expressing c-myc under the control of the albumin promoter and enhancer develop liver tumors and have served as a useful model for studying the progression of hepatocarcinogenesis. The chromosomes of one line of c-myc transgenic mice carry the reciprocal translocation t(5;6)(G1;F2) adjacent to the transgene insertion site on the 5G1-ter segment translocated to chromosome 6. To characterize the genomic alterations in the c-myc transgenic animals, we have cloned the mouse DNA flanking the transgene array. By linkage mapping, the transgene integration site was localized to the region of distal chromosome 5 syntenic to the region on human chromosome 7q11.23 that is hemizgygously deleted in Williams-Beuren syndrome, a multisystemic developmental disorder. Comparison of the genomic DNA structure in wildtype and transgenic mice revealed that the transgene integration had induced an approximately 40-kb deletion, starting downstream of the Cyln2 gene and including the first exon of the Gtf2ird1 gene. Gtf2ird1 encodes a polypeptide related to general transcription factor TFII-I, and it is the mouse orthologue of GTF2IRD1 (WBSCR11), one of the genes commonly deleted in Williams-Beuren syndrome patients. Loss of the 5' end of the Gtf2ird1 gene resulted in greatly reduced expression of Gtf2ird1 mRNA in mice homozygous for the transgene.
authors.affiliation: Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. marian_durkin@nih.gov
authors.forename: M E
authors.initials: ME
authors.lastname: Durkin
authors.forename: C L
authors.initials: CL
authors.lastname: Keck-Waggoner
authors.forename: N C
authors.initials: NC
authors.lastname: Popescu
authors.forename: S S
authors.initials: SS
authors.lastname: Thorgeirsson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods; D002897:Chromosomes, Human, Pair 7; D004247:DNA; D005091:Exons; D017353:Gene Deletion; D015870:Gene Expression; D016259:Genes, myc; D008040:Genetic Linkage; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes; D014178:Translocation, Genetic; D018980:Williams Syndrome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA