The ldis1 lens mutation in RIIIS/J mice maps to chromosome 8 near cadherin 1.
The ldis1 lens mutation in RIIIS/J mice maps to chromosome 8 near cadherin 1.
复制标题
DOI：
--
复制
发表时间：
2004-08
期刊：
影响因子：
2.2
通讯作者：
M. Jablonski;Lu Lu-Lu;Xiaofei F Wang;E. Chesler;Emily Carps;Shuhua Qi;Jing Gu;Robert W. Williams
中科院分区：
文献类型：
--
作者：
M. Jablonski;Lu Lu-Lu;Xiaofei F Wang;E. Chesler;Emily Carps;Shuhua Qi;Jing Gu;Robert W. Williams
目的 我们发现了一种自发且严重的突变，该突变会导致 RIIIS/J 近交系小鼠的晶状体部分或完全破坏和白内障。本研究的目的是利用组织学、眼科、定量电子显微镜和基于微阵列的方法确定遗传模式、特异性和表型范围。我们还对突变 ldis1（晶状体破坏者 1）进行了精细定位，并评估了位置候选基因。方法 对突变型 RIIIS/J 动物以及 RIIIS/J 和 DBA/2J 杂交 F2 动物的眼睛进行检查和评分，以绘制 ldis1 突变图谱。计算视神经中的轴突。来自突变眼的信使 RNA 与 Affymetrix 短寡聚体微阵列杂交，并与五种对照菌株进行比较。表达差异用于评估突变的分子后遗症。结果 ldis1 纯合子小鼠的眼睛较小。晶状体无一例外都是不透明的、变形的、错位的、碎片的和小的。相反，视网膜结构和神经节细胞数量在正常范围内。我们尚未检测到任何其他 ldis1 相关的眼部或全身异常。 ldis1 是隐性的，映射到 D8Mit242 和 D8Mit199 之间约 106.5 Mb 的 8 号染色体，LOD 得分峰值接近钙粘蛋白 1。同源人类染色体间隔为 16q22.1。几个下游晶状体蛋白转录物的表达在突变体中受到严重影响，转化生长因子超家族和谷胱甘肽S-转移酶的多个成员的表达水平也受到严重影响。结论 我们发现并定位了小鼠 8 号染色体 105 至 109 Mb 之间的隐性突变。纯合突变小鼠对晶状体完整性具有选择性和严重影响。根据表型和基因座位置，已经鉴定了几个候选基因。
PURPOSE We have discovered a spontaneous and severe mutation that leads to partial or complete disruption of the lens and cataract in the RIIIS/J inbred strain of mice. The purpose of this study was to determine the mode of inheritance, specificity, and range of phenotypes using histological, ophthalmic, quantitative electron microscopic, and microarray-based methods. We also have fine-mapped the mutation, ldis1 (lens disrupter 1), and have evaluated positional candidate genes. METHODS Eyes from mutant RIIIS/J animals and from an F2 intercross between RIIIS/J and DBA/2J were examined and scored to map the ldis1 mutation. Axons in the optic nerve were counted. Messenger RNA from mutant eyes was hybridized to Affymetrix short oligomer microarrays and compared to five control strains. Expression differences were used to evaluate molecular sequellae of the mutation. RESULTS Mice that are homozygous for ldis1 have small eyes. Lenses are without exception opaque, deformed, dislocated, fragmented, and small. In contrast, retinal architecture and ganglion cell numbers are within normal range. We have not detected any other ldis1-associated ocular or systemic abnormalities. ldis1 is recessive and maps to chromosome 8 at about 106.5 Mb between D8Mit242 and D8Mit199 with a peak LOD score near cadherin 1. The homologous human chromosomal interval is 16q22.1. The expression of several downstream crystallin transcripts are severely affected in the mutant, as are the expression levels of multiple members of the transforming growth factor superfamily and the glutathione S-transferases. CONCLUSIONS We have discovered and mapped a recessive mutation to mouse chromosome 8 between 105 and 109 Mb. Homozygous mutant mice have a selective and severe effect on lens integrity. On the basis of the phenotype and the locus position, several candidate genes have been identified.