CLONING OF A CDNA-ENCODING A PUTATIVE HUMAN VERY-LOW-DENSITY LIPOPROTEIN APOLIPOPROTEIN-E RECEPTOR AND ASSIGNMENT OF THE GENE TO CHROMOSOME-9PTER-P23

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Norther n analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb wit h most abundant expression in heart and skeletal muscle, followed by k idney, placenta, pancreas, and brain. The pattern of expression genera lly paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipo protein receptor-related protein/alpha2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE recept or mRNA was induced during the transformation of the cells into adipoc ytes. Expression was also detected in human choriocarcinoma cells, sug gesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Ex pression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypo thesized role for ApoE in late onset Alzheimer disease. Our results su ggest that the putative VLDL/ApoE receptor could play a role in the up take of triglyceride-rich lipoprotein particles by specific organs inc luding striated and cardiac muscle and adipose tissue and in the trans port of maternal lipids across the placenta. The findings presented he re, together with recent observations from other laboratories, bring u p the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzhe imer disease, and obesity.