A number of retinal diseases are associated with defects in the CRX (cone-rod homeobox) gene, which encodes a transcription factor required for development and maintenance of photoreceptor cells. See links in 'Related Diseases' for information on specific diseases. There is a single fly ortholog, Dmel\oc, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\oc is orthologous to two additional human genes, OTX1 and OTX2.
A number of genes associated with retinal disease are implicated in multiple related diseases, such as retinitis pigmentosa, cone-rod dystrophy, and forms of macular degeneration. In some cases, a single molecular variant is implicated in more than one form of retinal disease. CRX is implicated in cone-rod dystrophy 2 (MIM:120970; FBhh0000569), Leber congenital amaurosis 7 (MIM:613829; FBhh0000565), and retinitis pigmentosa (see MIM:268000; FBhh0000186).
Multiple UAS constructs of the human Hsap\CRX gene have been introduced into flies, including wild-type and variants associated with cone-rod dystrophy 2 (CRD2) and Leber congenital amaurosis 7 (LCA7). Heterologous rescue (functional complementation) has been demonstrated for the morphological defects of the photoreceptor cells exhibited by alleles of Dmel\oc; most, but not all, of the transcriptional regulatory functions assayed are also rescued.
Variant(s) implicated in human disease tested (as transgenic human gene, CRX): the R90W and K88N variant forms (implicated in LCA7), the c.413delT(p.I138fs48) C-terminal deletion (implicated in LCA7), and the E80A variant form (implicated in CRD2) have been introduced into flies.
The original allele of Dmel\oc, when homozygous, causes loss of the ocelli (simple visual organs on the top of the adult head); more severe alleles result in morphological defects in the rhabdomeres of the adult eye; amorphic alleles are lethal in the embryonic stage. Physical and genetic interactions of Dmel\oc have been described; see below and in the gene report for oc.
[updated Jun. 2017 by FlyBase; FBrf0222196]
CRX is implicated in cone-rod retinal dystrophy-2 (CORD2) and Leber congenital amaurosis 7 (LCA7). [from MIM:602225; 2017.06.29] There is some evidence that it is also implicated in retinitis pigmentosa (Sohocki et al., 2001; pubmed:1113924).[from MIM:268000; 2017.06.29]
CRX (cone-rod homeobox) is essential for the maintenance of mammalian photoreceptors. [Gene Cards, CRX; 2017.06.29]
CRX encodes a photoreceptor-specific transcription factor and plays a crucial role in the differentiation of photoreceptor cells (Furukawa et al, 1997; pubmed:9390562). [from MIM:602225; 2017.06.29]
Many to one: 3 human to one Drosophila; the other human genes are OTX1 and OTX2.
Low- to moderate-scoring ortholog of human genes OTX1, OTX2, and CRX (1 Drosophila to 3 human); Dmel\oc shars 30-36% identity and 40-45% similarity with the human genes.
