Genomic evidence for the absence of a functional cholesteryl ester transfer protein gene in mice and rats.
Mice and rats are naturally deficient in cholesteryl ester transfer protein (CETP) activity, although the reason behind the deficiency in activity is unknown. A search of mouse genome databases revealed sequences resembling 7 of the 16 human exons. However, these sequences could not code for a functional CETP. Analysis of the rat genome using Southern blotting revealed sequences complementary to human CETP cDNA, but RNase protection assays were unable to detect any Cetp gene expression in liver, adipose, or muscle. A search of rat whole-genome shotgun databases revealed exon-like sequences that would be unable to code for a functional CETP. An Ap3s1 pseudogene lay immediately upstream of the CETP-like sequences in mouse, but was nearly identical to the functional gene and unlikely to have been inserted prior to mouse-rat divergence. In contrast, a deletion leading to a nonsense codon was found in the exon 11-like sequences of both rat and mouse and not in any other species. Thus, the lack of CETP activity in both the mouse and the rat is most likely due to an evolutionary event that occurred before these species diverged and not to altered regulation of the gene or function of the gene product.
Hogarth
Cathryn A
CA
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Roy
Alison
A
Ebert
David L
DL
D033963:Adaptor Protein Complex 3; D034002:Adaptor Protein Complex sigma Subunits; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D020868:Gene Silencing; D016678:Genome; D006023:Glycoproteins; D006801:Humans; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D011817:Rabbits; D051381:Rats / Q000235:genetics*; D016415:Sequence Alignment; D013552:Swine
C115637:AP3S1 protein, human; D033963:Adaptor Protein Complex 3; D034002:Adaptor Protein Complex sigma Subunits; C485460:Ap3s1 protein, mouse; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins