|Freking, Bradley - Brad|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/2/2001
Publication Date: 6/2/2001
Citation: Motaln, H., Freking, B.A., Medrano, J.F., Horvat, S. 2001. Transcript mapping of the 500-kb high growth (hg) region in mice [abstract]. The 15th International Mouse Genome Conference, Bled, Slovenia. P. 39, Poster #169.
Technical Abstract: The high growth (hg) mutation in mouse is characterized by a 30-50% increase in weight gain and mature body size. High growth (HG) mice grow more efficiently, are not obese, exhibit muscle fiber hyperplasia and a proportional increase of organs and skeleton. Our previous genetic and physical mapping studies have shown that hg maps to a deletion of ~500-kb (hg region) on mouse chromosome 10. Using positional cloning strategy, we have recently identified that the molecular cause for the high growth phenotype is lack of Socs2 expression, a gene that is disrupted by one of the deletion breakpoints in the hg region. To identify other genes that lie within the hg region, we have employed comparative mapping, exon trapping, and direct sequencing. For comparative mapping, 56 human expressed sequence tag (EST) clones from a region on human chromosome 12 that is homologous to the mouse hg region were selected and hybridized to five mouse BAC probes spanning the hg region. Ten candidate human ESTs were identified, which no need to be studied further using sequence and expression analyses to identify true orthologs. A second approach of exon trapping involved isolation of potential exon sequences within the mouse BAC clones. A total of 24 exon traps gave positive RT-PCR signal in at least one of the studied tissues. Sequence homology analyses showed that some exon traps belong to one of the three known genes within the hg region, Vespr, Raidd, and Socs2, while some may present novel transcription units. A third approach of direct sequencing and searching for genes with computer-based approaches (BLAST, GRAIL) is also underway. Using the above three approaches it should be possible to characterize all the genes within the 500-kb deletion to permit further functional characterization studies of the hg deletion.