Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice.
Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice.
复制标题
DOI：
--
复制
发表时间：
2001-11
期刊：
影响因子：
2.2
通讯作者：
Guomin Zhou;R. C. Strom;Vincent Giguère;Robert W. Williams
中科院分区：
文献类型：
--
作者：
Guomin Zhou;R. C. Strom;Vincent Giguère;Robert W. Williams
目的视黄酸受体在脊椎动物眼的不同组织中从发育的早期阶段开始表达。他们的损失对眼睛的发育有微妙的影响。我们采用敏感的数量性状基因座（QTL）作图方法来评估α和β受体Rara和Rarb的等位基因失活对眼睛和视网膜发育的影响。Rara是特别感兴趣的，因为该基因是Nnc 1的候选基因，Nnc 1是控制视网膜神经节细胞增殖的QTL。方法：我们研究了小鼠品系，其中Rara的a1亚型或Rarb的所有亚型的表达已被基因靶向破坏。我们测量了6种基因型（Rara和Rarb -/-、+/-、+/+; 10-25例/基因型）中每种基因型的眼重、透镜重、视网膜面积和视网膜神经节细胞数。结果任一蛋白质的缺失都与眼重和视网膜面积的小但显著的损失相关。然而，只有Rarb敲除对神经节细胞群体具有显著影响，并且两个野生型等位基因的丢失导致8，000个细胞的缺陷。令人惊讶的是，从早期阶段在该细胞群中表达的Rara a1同种型的损失对数量没有影响。两个基因的等位基因对透镜生长几乎没有影响。结论：尽管Rara在胚胎视网膜中表达，但它不太可能是Nnc 1 QTL。与此相反，Rarb，一个基因，映射到Chr 14，这不是一个Nnc 1候选基因，有一个显着的影响细胞数，因此是一个QTL控制这个关键群体。这提出了一种有趣的可能性，即Rarb的正常等位基因变体调节其他脊椎动物（包括人类）的神经节细胞群。
PURPOSE The retinoic acid receptors are expressed from early stages of development in the diverse tissues that make up the vertebrate eye. Their loss has subtle effects on eye development. We adapted sensitive quantitative trait locus (QTL) mapping methods to assess consequences of inactivating alleles of the alpha and beta receptors, Rara and Rarb, on eye and retinal development. Rara is of particular interest because this gene is a candidate for Nnc1, a QTL that controls retinal ganglion cell proliferation. METHODS We studied lines of mice in which expression of the a1 isoform of Rara or all isoforms of Rarb had been disrupted by gene targeting. We measured eye weight, lens weight, retinal area, and retinal ganglion cell number in each of six genotypes (Rara and Rarb -/-, +/-, +/+; 10-25 cases/genotype). RESULTS Loss of either protein is associated with a small but significant loss of eye weight and retinal area. However, only the Rarb knockout has a significant effect on the ganglion cell population and the loss of both wildtype alleles leads to an 8,000 cell deficit. Surprisingly, loss of the Rara a1 isoform that is expressed in this cell population from early stages has no effect on number. Null alleles of both genes have little if any effect on lens growth. CONCLUSIONS Despite its expression in embryonic retina, Rara is unlikely to be the Nnc1 QTL. In contrast, Rarb, a gene that maps to Chr 14 and which is not an Nnc1 candidate gene, has a significant effect on cell number and is therefore a QTL controlling this key population. This raises the intriguing possibility that normal allelic variants of Rarb modulate the ganglion cell population in other vertebrates, including humans.