Transgenic Mice Research Based On BAC Containing The Entire Human Apolipoprotein A-Ⅰ C-Ⅲ A-Ⅳ A-Ⅴ Gene Cluster

The human apolipoprotein family consists of 19 members and the majority locate in five different chromosomes. The apoA-II, apoB, apo (a) gene locate on the long arm of chromosome 1, the short arm of chromosome 2 and the long arm of chromosome 6, respectively. The apoA-I C-III A-IV A-V and apoE C-I C-IV C-II gene cluster locates on the long arm of chromosome 11 and chromosome 19, respectively.In the apoA-I C-III A-IV A-V gene cluster the transcriptional direction of apoC-III is opposite to the others. The apoC-III gene enhancer may be the common regulatory element for apoA-I, C-III and A-IV. The apoA-I, C-III, A-V mainly express in the liver in vivo, whereas the apoA-IV mainly expresses in the intestine. The expressions of apolipoproteins maitain balance and regulate the metabolism of lipids in the plasma.Studies of statement regulation of eukaryotic genes in transgenic mice permit not only the devices of experiments on molecular level but also the observation of the involvement of almost all the factors affecting gene statement and investigations of in vivo effect of gene regulations. Transgenic technique can be applied to set up transgenic models for human genetic diseases from which statement regulation of abnormal genes are demonstrated and many pre-clinical data for human gene therapy will be provided. The cosmid and yeast artificial chromosome (YAC) system can be combined with transgenic technique to investigate the developmental regulation of large gene clusters. There are several limitations in the system. First, it is difficult to isolate intact YAC DNA. Second,...