Battinelli E M, Boyd Y, Craig I W, Breakefield X O, Chen Z Y
Molecular Neurogenetics Laboratory, Massachusetts General Hospital, East, Charlestown 02129, USA.
Mamm Genome. 1996 Feb;7(2):93-7. doi: 10.1007/s003359900026.
Norrie disease is a severe X-linked recessive neurological disorder characterized by congenital blindness with progressive loss of hearing. Over half of Norrie patients also manifest different degrees of mental retardation. The gene for Norrie disease (NDP) has recently been cloned and characterized. With the human NDP cDNA, mouse genomic phage libraries were screened for the homolog of the gene. Comparison between mouse and human genomic DNA blots hybridized with the NDP cDNA, as well as analysis of phage clones, shows that the mouse NDP gene is 29 kb in size (28 kb for the human gene). The organization in the two species is very similar. Both have three exons with similar-sized introns and identical exon-intron boundaries between exon 2 and 3. The mouse open reading frame is 393 bp and, like the human coding sequence, is encoded in exons 2 and 3. The absence of six nucleotides in the second mouse exon results in the encoded protein being two amino acids smaller than its human counterpart. The overall homology between the human and mouse NDP protein is 95% and is particularly high (99%) in exon 3, consistent with the apparent functional importance of this region. Analysis of transcription initiation sites suggests the presence of multiple start sites associated with expression of the mouse NDP gene. Pedigree analysis of an interspecific mouse backcross localizes the mouse NDP gene close to Maoa in the conserved segment, which runs from CYBB to PFC in both human and mouse.
诺里病是一种严重的X连锁隐性神经疾病，其特征为先天性失明并伴有进行性听力丧失。超过半数的诺里病患者还表现出不同程度的智力迟钝。诺里病基因（NDP）最近已被克隆和鉴定。利用人类NDP cDNA，对小鼠基因组噬菌体文库进行该基因同源物的筛选。用NDP cDNA杂交的小鼠和人类基因组DNA印迹比较，以及噬菌体克隆分析表明，小鼠NDP基因大小为29 kb（人类基因为28 kb）。这两个物种的基因结构非常相似。两者都有三个外显子，内含子大小相似，外显子2和3之间的外显子-内含子边界相同。小鼠开放阅读框为393 bp，与人类编码序列一样，由外显子2和3编码。小鼠第二个外显子中缺少六个核苷酸，导致编码的蛋白质比人类对应蛋白质少两个氨基酸。人类和小鼠NDP蛋白的总体同源性为95%，在外显子3中尤其高（99%），这与该区域明显的功能重要性一致。转录起始位点分析表明存在与小鼠NDP基因表达相关的多个起始位点。种间小鼠回交的系谱分析将小鼠NDP基因定位在保守区段中靠近单胺氧化酶A的位置，该保守区段在人类和小鼠中均从细胞色素b-245β链基因延伸至血小板因子4。
