IDENTIFICATION OF A NONSENSE MUTATION IN THE ROD PHOTORECEPTOR CGMP PHOSPHODIESTERASE BETA-SUBUNIT GENE OF THE RD MOUSE
IDENTIFICATION OF A NONSENSE MUTATION IN THE ROD PHOTORECEPTOR CGMP PHOSPHODIESTERASE BETA-SUBUNIT GENE OF THE RD MOUSE
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DOI：
10.1073/pnas.88.19.8322
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
BAEHR, W
中科院分区：
文献类型：
--
作者：
PITTLER, SJ;BAEHR, W
小鼠突变体rd的视网膜变性先前被证明是涉及视杆细胞cGMP磷酸二酯酶（PDE）活性缺乏的环核苷酸代谢障碍。我们的特点是正常和rd PDE β亚基基因，和他们各自的成绩单，通过PCR和直接序列分析。我们发现，该基因由至少22个外显子组成，大小从48个碱基对到几百个碱基对不等，覆盖> 25个酶。在rd PDE β亚基基因的67个碱基对外显子中，我们发现了一个无义赭石突变（密码子347中的C -> A颠换），该突变截断了正常的基因产物，消除了超过一半的肽链，包括推定的催化结构域。截短的结果与在rd小鼠中观察到的该疾病的杂合子和纯合子的表型一致。无义突变也被发现在另一个相关的和六个无关的菌株显示rd表型，表明rd等位基因来自一个单一的遗传事件。这些结果有力地证明了无义突变是rd小鼠视网膜变性的原因。
Retinal degeneration in the mouse mutant, rd, was previously shown to be a disorder of cyclic nucleotide metabolism involving a deficiency in the activity of the rod photoreceptor cGMP phosphodiesterase (PDE). We have characterized the normal and rd PDE beta-subunit gene, and their respective transcripts, by PCR and direct sequence analysis. We show that the gene consists of at least 22 exons ranging in size from 48 base pairs to several hundred base pairs, covering > 25 kilobases. Within a 67-base-pair exon of the rd PDE beta-subunit gene, we identified a nonsense ochre mutation (a C --> A transversion in codon 347) that truncates the normal gene product, eliminating more than one-half of the peptide chain, including the putative catalytic domain. The consequences of the truncation are consistent with the observed phenotypes in rd mice heterozygous and homozygous for the disorder. The nonsense mutation was also found in another related and in six unrelated strains displaying the rd phenotype, indicating that the rd allele arose from a single genetic event. The results strongly argue for the nonsense mutation being responsible for retinal degeneration in the rd mouse.