RECENT DEVELOPMENT IN THE SEARCH FOR THE MOUSE high growth (hg) GENE

¹ Department of Animal Science, University of California, Davis, CA 95616-8521, USA

² Division of Molecular Biology, Roslin Institute (Edinburgh), Roslin, EH25 9PS, Scotland, UK

The mouse high growth (hg) gene produces a 30-50% increase in weight gain of homozygous individuals without resulting in obesity. High growth mice have an increased muscle mass primarily due to muscle fiber hyperplasia, with moderate hypertrophy; elevated concentrations of insulin growth factor-1 (IGF-1), and decreased plasma levels of growth hormone. Using interval mapping, test crosses and fine mapping, in a C57BL/6J-hghg congenic strain, hg was mapped to a deletion in the distal portion of mouse chromosome 10 between the igf-1 and decorin genes. A deleted microsatellite, D10Mit69, was utilized as an entry point to physical cloning of the hg-containing segment using Yeast Artificial Chromosome (YAC) and Bacterial Artificial Chromosome (BAC) clones. A physical map of YAC and BAC clones spanning a 500-kb region deleted in high growth mice was constructed. Exon trapping of the BAC clones was used to uncover expressed sequences. EST and cDNA analysis of an exon-trapping product led to the identification of the murine Raidd/Cradd gene as a potential candidate for hg. Raidd/Cradd is a protein that serves as an adaptor molecule for death proteases in the apoptotic-signaling pathway. Therefore, it may be possible that the increase in cell number observed in high-growth may be the result of alterations in the apoptosis pathway. Determination of the causality of Raidd/Cradd and high-growth will come from transgenic studies. These studies are underway, as well as random sequencing of the hg-deleted region to identify other possible genes that may be found within this region.