Van Leuven F, Stas L, Hilliker C, Lorent K, Umans L, Serneels L, Overbergh L, Torrekens S, Moechars D, De Strooper B
Experimental Genetics Group, Center for Human Genetics, K. U. Leuven, Belgium.
Genomics. 1994 Nov 1;24(1):78-89. doi: 10.1006/geno.1994.1584.
The alpha 2-macroglobulin receptor or lipoprotein receptor-related protein (A2MR/LRP) is an amazingly large and multifunctional receptor. The active receptor protein is derived from a 600-kDa precursor, encoded by a 15-kb mRNA, cloned and sequenced in human, mouse, and chicken. We report here the cloning of the entire human gene (LRP1) coding for A2MR/LRP. The gene covered about 92 kb and a total of 89 exons were identified, varying in size from 65 bases (exon 86) to 925 bases (exon 89). The introns varied from 82 bases (intron 53) to about 8 kb (intron 6). In the introns, 3 complete and 4 partial Alu sequences were identified. In intron 44 a complex repetitive sequence posed a cloning problem since it was not retrieved from any genomic library screened. Interexon PCR from exon 43 to 45 yielded a fragment of 2.5 kb. Attempts to subclone this fragment yielded inserts ranging between 0.8 and 1.6 kb. Sequencing of 3 subclones with different-size inserts revealed a complex repetitive element with a different size in each subclone. In the mouse LRP gene this intron was much smaller, and no repetitive sequence was observed. In 18 unrelated individuals no difference in size was observed when analyzed by interexon PCR.
α2-巨球蛋白受体或脂蛋白受体相关蛋白（A2MR/LRP）是一种极其庞大且多功能的受体。活性受体蛋白源自一个600 kDa的前体，由一个15 kb的mRNA编码，已在人、小鼠和鸡中进行了克隆和测序。我们在此报告编码A2MR/LRP的整个人类基因（LRP1）的克隆。该基因覆盖约92 kb，共鉴定出89个外显子，大小从65个碱基（外显子86）到925个碱基（外显子89）不等。内含子大小从82个碱基（内含子53）到约8 kb（内含子6）不等。在内含子中，鉴定出3个完整的和4个部分的Alu序列。在内含子44中，一个复杂的重复序列给克隆带来了问题，因为在筛选的任何基因组文库中都未检索到它。从外显子43到45进行外显子间PCR产生了一个2.5 kb的片段。尝试亚克隆该片段得到的插入片段大小在0.8至1.6 kb之间。对3个具有不同大小插入片段的亚克隆进行测序，发现每个亚克隆中都有一个大小不同的复杂重复元件。在小鼠LRP基因中，这个内含子要小得多，并且未观察到重复序列。在18个不相关的个体中，通过外显子间PCR分析时未观察到大小差异。
