Dhar Madhu, Hauser Loren, Johnson Dabney
The University of Tennessee Graduate School of Genome Science and Technology, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.
Obes Res. 2002 Jul;10(7):695-702. doi: 10.1038/oby.2002.94.
We have shown that a region on proximal mouse chromosome 7, near the pink-eyed (p) dilution locus, contains an ATPase (pfatp), a putative aminophospholipid translocase. Studies have suggested that this gene is a prime candidate for modulating body fat or involved in lipid metabolism in mouse and humans. Toward further analyses, our objective was to generate the complete genomic structures of mouse and human genes.
The genomic structure of mouse pfatp was deduced by comparing the full-length cDNA sequence with the genomic sequence derived from a mouse BAC. The human ortholog was identified from the National Center for Biotechnology Information database. Full-length cDNA was generated, and the corresponding genomic structure was deduced from the Human Genome Database.
Murine pfatp, and its human ortholog, PFATP, belong to class V of the third subfamily of P-type ATPases. The gene organization is strikingly similar in both organisms and all exon-intron junctions are conserved. A putative promoter region of PFATP contains a strong CpG island. The 5' untranslated regions of the two cDNAs have potential binding sites for multiple transcription factors, including Sp1, USF, AP1, and AP2, involved in adipogenesis and adipocyte metabolism.
We report the generation of the complete genomic structure of a novel aminophospholipid translocase in mice and humans. Because the exact biological role and the subsequent relevance of these ATPases to obesity and diabetes are unknown, these data help to delineate the role of these genes in lipid/adipocyte metabolism.
我们已经证明，在近端小鼠7号染色体上靠近粉红眼（p）稀释位点的一个区域包含一种ATP酶（pfatp），一种假定的氨基磷脂转位酶。研究表明，该基因是调节小鼠和人体脂肪或参与脂质代谢的主要候选基因。为了进一步分析，我们的目标是生成小鼠和人类基因的完整基因组结构。
通过将全长cDNA序列与来自小鼠BAC的基因组序列进行比较，推导小鼠pfatp的基因组结构。从美国国立生物技术信息中心数据库中鉴定出人类直系同源基因。生成全长cDNA，并从人类基因组数据库中推导相应的基因组结构。
小鼠pfatp及其人类直系同源基因PFATP属于P型ATP酶第三个亚家族的V类。两种生物的基因组织惊人地相似，所有外显子-内含子连接均保守。PFATP的一个假定启动子区域包含一个强CpG岛。两种cDNA的5'非翻译区具有多个转录因子的潜在结合位点，包括参与脂肪生成和脂肪细胞代谢的Sp1、USF、AP1和AP2。
我们报告了小鼠和人类中一种新型氨基磷脂转位酶完整基因组结构的生成。由于这些ATP酶的确切生物学作用以及它们与肥胖和糖尿病的后续相关性尚不清楚，这些数据有助于阐明这些基因在脂质/脂肪细胞代谢中的作用。
