Level of expression and chromosome mapping of the mouse cholecystokinin gene: implications for murine models of genetic obesity.
Cholecystokinin (CCK) is a neuropeptide which is present in brain and intestine and which stimulates gall bladder contraction and pancreatic secretion. Additional studies have demonstrated an appetite-suppressing effect of CCK in vivo. These data have aroused speculation that the physiology of this hormone could be relevant in the pathogenesis of the mouse obesity mutations ob on chromosome 6 and db on chromosome 4. In order to determine whether abnormalities of this hormone could be the primary defect in these obesity mutations, we have used three separate approaches to map the mouse Cck gene to distal chromosome 9, where it is part of a syntenic group between mouse chromosome 9 and human chromosome 3. These data therefore exclude cholecystokinin as the etiologic factor in the pathogenesis of any of the known mouse obesity syndromes. In order to exclude the possibility that there are differences in mutant animals in the level of CCK RNA, we have used an S1 nuclease protection assay as well as a novel radioimmunoassay that detects the CCK precursor, to show that there are no gross differences in CCK mRNA or protein precursor levels between ob/ob and wild-type animals.
Friedman
J M
JM
Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021.
Schneider
B S
BS
Barton
D E
DE
Francke
U
U
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D002766:Cholecystokinin / Q000235:genetics*; D002874:Chromosome Mapping; D006224:Cricetinae; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006822:Hybrid Cells; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger; D011863:Radioimmunoassay; D051381:Rats
D011498:Protein Precursors; D012333:RNA, Messenger; D004247:DNA; D002766:Cholecystokinin