|Freking, Bradley - Brad|
Submitted to: Mouse Genome Conference
Publication Type: Abstract only
Publication Acceptance Date: 7/25/1999
Publication Date: N/A
Citation: Horvat, S., McWhir, J., Freking, B.A., Medrano, J.F. 1999. Isolation and evaluation of candidate genes for the high growth (hg) mutation in mice [abstract]. The 13th International Mouse Genome Conference, Philadelphia, PA, October 31-November 3, 1999. #F28. Interpretive Summary:
Technical Abstract: The high growth (hg) mutation in mouse presents a unique model because of its large effect on growth. It is characterized by a 30-50% increase in weight gain and mature body size in homozygous individuals. High growth mice grow more efficiently than controls and are not obese. The increase in body size in high growth mice is accompanied by an increase in muscle mass, due primarily to fiber hyperplasia and a moderate hypertrophy. The increase of organs and skeleton is proportional. Previous genetic analyses located hg on mouse chromosome 10 and demonstrated that hg is not an allele of insulin-like growth factor I or Decorin, two closely linked candidates. A microsatellite marker D10Mit69 from the candidate genetic interval was found to be deleted in high growth mice and used as a starting probe for chromosomal walking within the hg-containing segment. The entire deletion was spanned using Yeast Artificial Chromosome and Bacterial Artificial Chromosome (BAC) clones and estimated to be approximately 500-kb long. Exon trapping of BACs, comparative mapping using human expressed sequence tags and random sequence scanning of BACs have been used to uncover expressed sequences within the hg candidate region. Identification of an exon-trapping product led to the isolation of the murine Raidd cDNA that maps within the high-growth deletion. Raidd is an adaptor molecule for death proteases in the apoptotic-signaling pathway that may potentially have a role in regulation of cell numbers and, consequently, the size of the organism. To determine whether a deletion of Raidd is responsible for the high-growth phenotype, we have initiated a knockout experiment of Raidd. The status of this transgenic experiment as well as the status of transcription mapping in the hg region will be presented.