Graw Jochen, Neuhäuser-Klaus Angelika, Löster Jana, Favor Jack
National Research Center for Environment and Health (Forschungszentrum für Umwelt und Gesundheit), Institute of Mammalian Genetics, Neuherberg, Germany.
Invest Ophthalmol Vis Sci. 2002 Jan;43(1):236-40.
A mouse mutant expressing a bilateral nuclear and radial cataract was found after paternal treatment with chlorambucil. The purpose of this study was to establish the linkage of the mutation to a particular chromosome to allow molecular characterization. Moreover, the mutants were examined morphologically.
Isolated lenses were photographed and histologic sections of the eye were analyzed according to standard procedures. The mutation was localized to chromosome 1 by allelism testing with the Cryge(nz) mutation. Candidate genes were amplified by PCR from cDNA or genomic DNA and sequenced.
A novel mouse cataract was characterized by a nuclear and radial opacification of the lens. The lenses of the mutants are smaller than those of the wild type. The histologic analysis demonstrated degeneration of lens fibers in the lens core. Abnormal remnants of cell nuclei are present throughout the entire lens. Genetic analysis revealed allelism to the Cat2 group of dominant cataracts on mouse chromosome 1; therefore, the cluster of the Cryg genes and the closely linked Cryba2 gene were tested as candidates. A 6-bp deletion in exon 3 of the gammaC-crystallin encoding gene (Crygc) is causative for the cataract phenotype; the mutation is therefore designated CrygcChl3. The deletion of the bases 420 to 425 leads to a loss of two amino acids, Gly and Arg, in the fourth Greek-key motif.
The CrygcChl3 is the first mutation in the mouse affecting the Crygc gene. Dominant mutations for five of the six Cryg genes on mouse chromosome 1 have now been characterized, demonstrating the importance of this gene cluster for lens transparency.
在用苯丁酸氮芥对父本进行处理后，发现了一只表现出双侧核性和放射状白内障的小鼠突变体。本研究的目的是确定该突变与特定染色体的连锁关系，以便进行分子特征分析。此外，还对突变体进行了形态学检查。
对分离出的晶状体进行拍照，并按照标准程序分析眼睛的组织学切片。通过与Cryge(nz)突变进行等位性测试，将该突变定位到1号染色体上。通过PCR从cDNA或基因组DNA中扩增候选基因并进行测序。
一种新的小鼠白内障的特征是晶状体出现核性和放射状混浊。突变体的晶状体比野生型的小。组织学分析表明晶状体核心的晶状体纤维发生退化。整个晶状体中都存在细胞核的异常残余物。遗传分析显示与小鼠1号染色体上的Cat2显性白内障组存在等位性；因此，对Cryg基因簇和紧密连锁的Cryba2基因进行了候选测试。编码γC-晶状体蛋白的基因（Crygc）外显子3中的6个碱基缺失是导致白内障表型的原因；因此，该突变被命名为CrygcChl3。420至425位碱基的缺失导致第四个希腊钥匙基序中两个氨基酸甘氨酸和精氨酸的缺失。
CrygcChl3是小鼠中影响Crygc基因的首个突变。现已鉴定出小鼠1号染色体上六个Cryg基因中五个的显性突变，证明了该基因簇对晶状体透明度的重要性。
