Table 1 |.
Clinical phenotypes caused by mutations in key transcriptional regulators of photoreceptor development
| Gene | Transcription factor type | Human diseases | Mouse mutant phenotypes |
|---|---|---|---|
| CRX | Paired-type homeodomain | Autosomal dominant cone–rod dystrophy; autosomal dominant and recessive Leber’s congenital amaurosis; autosomal dominant retinitis pigmentosa | Lack of outer segments in rods and cones; circadian entrainment defect; impaired bipolar cell differentiation and maintenance |
| NRL | Maf family basic leucine zipper | Autosomal dominant and recessive retinitis pigmentosa | Complete loss of rods; transformation of rods into S cones, with shorter outer segments than normal; enhanced S cone function; photoreceptor layer rosettes |
| NR2E3 | Orphan nuclear receptor | Enhanced S cone syndrome; autosomal dominant retinitis pigmentosa | Appearance of rod photoreceptors expressing cone genes; photoreceptor layer rosettes; retinal degeneration |
| OTX2 | Paired-type homeodomain | Microphthalmia (syndromic) | Loss of rods and cones and increase in amacrine-like neurons; loss of pinealocytes; impaired bipolar cell differentiation and maintenance; patterning abnormalities in the midbrain and hindbrain |
| RORB | Orphan nuclear receptor | None discovered | Loss of rods and over-production of S cones; lack of all outer segments; retinal disorganization; retarded induction of S opsin expression in cones; circadian behaviour abnormalities; abnormal gait |
| THRB | Thyroid hormone-activated nuclear receptor | Resistance to thyroid hormone, typically autosomal dominant; endocrine and neurological dysfunction; rare colour vision abnormalities | Loss of M opsin and extended distribution of S opsin in cones across the retina instead of normal bias in the ventral region; endocrine dysfunction; deafness |
CRX, cone–rod homeobox protein; NR2E3, photoreceptor-specific nuclear receptor; NRL, neural retina leucine zipper protein; THRB, thyroid hormone receptor β. Data are from the RetNet database (http://www.sph.uth.tmc.edu/retnet/), the OMIM database (http://www.ncbi.nlm.nih.gov/omim)) and from references in the main text.