Tg(Pklr-HRAS*G12V)21Ak

This transgene includes a 4.9-kb BamHI fragment containing the 4 exons of the human HRAS gene with a single amino acid substitution of a glycine to valine at codon 12 under the control of the regulatory regions of the rat L-type pyruvate kinase (1.46 kb of the 5' flanking sequence). In this construct, the distal activator sequence of Pklr located around position -3 kb is removed. The single amino-acid substitution produces a constitutively active product. The Pklr regulatory sequences confer positive transcriptional control by glucose so maximal expression of the transgene can be obtained under a carbohydrate-rich diet. Three lines were made, lines 11, 21, and 23. Four copies of the transgene were inserted into the genome in line 21 and Northern blot confirmed expression in kidney, small intestine, epididymis, and thymus. (J:44803)