CHARACTERIZATION AND TISSUE-SPECIFIC EXPRESSION OF THE HUMAN VERY-LOW-DENSITY LIPOPROTEIN (VLDL) RECEPTOR MESSENGER-RNA

A cDNA has been isolated from human heart that is homologous to a member of the low density lipoprotein (LDL) receptor gene family recently identified in rabbit. It was named the very low density lipoprotein (VLDL) receptor, although its physiological function is not yet known. The predicted human protein shows 97.4% sequence homology to the rabbit protein, much more than the approximately 75% observed between their LDL receptor proteins. The sequence is also highly conserved in the hamster and the African green monkey. The mRNA was identified as a 3.9 kb transcript by Northern blotting in Hep G2 cells, cultured arterial smooth muscle cells and human skin fibroblasts, where its level was unaffected by sterols. The mRNA was not detected in EBV-lymphoblasts or in monocyte-macrophages by Northern blotting or by RT-PCR. In human tissues in vivo, the mRNA was expressed predominantly in heart and skeletal muscle, and also in ovary and kidney, but not in the liver. Although the 3.9 kb mRNA was the major transcript, a larger variant of 5.2 kb was also detectable and was predominant in skeletal muscle. Amplification of the mRNA from cultured human cells also revealed a potential splice variant that lacked 84 bp coding for a region equivalent to the O-linked sugars domain of the LDL receptor. It was a minor component in most cell types, but was predominant in Hep G2 cells.