Table 1.
Zebrafish mutants and morphants with ocular phenotypes relevant to human disorders and associated pathologies. Due to space limitations, not all relevant mutant and morphant zebrafish are included in this table.
| Gene | Mutant / Morpholino |
Ocular Phenotype | References | Associated Human Ocular Disease* |
OMIM |
|---|---|---|---|---|---|
| Coloboma | |||||
| adenomatous polyposis coli (apc) | Mutant | Coloboma; defects in optic vesicle patterning and optic fissure closure | [98] | Familial Adenomatous Polyposis | 175100 |
| bcl6 co-repressor (bcor) | Morpholino | Coloboma; microphthalmia | [246] | Oculofaciocardiodental and Lenz microphthalmia | 300485 |
| cadherin 2 neuronal (cdh2, glass onion) | Mutant | Coloboma; optic fissure closure defect | [247] | — | — |
| laminin,β1 (lamb1, lamb1hi1113bTg), laminin,γ1 (lamc1, lamc1hi3890Tg) | Mutant | Coloboma; basement membrane defects | [105] | — | — |
| paired box gene 2a (pax2a, no isthmus) | Mutant | Coloboma | [81] | Renal-coloboma Syndrome | 167409 |
| patched1 (ptc1, blowout) | Mutant | Coloboma; defects in optic stalk morphogenesis | [84, 85] | — | — |
| thioredoxin-related transmembrane prtein 3 (tmx3) | Morpholino | Microphthalmia; coloboma | [248] | Microphthalmia and coloboma | — |
| transcription factor ap2 alpha (tfap2a) | Morpholino | Coloboma | [249] | Branchio-Oculo-Facial Syndrome | 107580 |
| zinc family member 2a (zic2a) | Morpholino | Coloboma; defects in optic stalk morphogenesis and optic vesicle patterning | [88] | — | — |
| zinc finger proteins 703 and 503 (znf703,503, also known as nlz1 and nlz2) | Morpholino | Coloboma; defects in optic vesicle patterning and optic fissure closure | [79] | — | — |
| Photoreceptors | |||||
| cone transducin α (tcα, no optokinetic response f) | Mutant | Reduced sensitivity to light by cones | [250] | — | — |
| crumbs homolog 2 (crb2, oko meduzy) | Mutant | Photoreceptor defects | [119] | — | — |
| crumbs homolog 2, like (crb2l) | Morpholino | Photoreceptor defects | [119] | — | — |
| dihydrolipoamide S-acetyltransferase (pdhe2, no optokinetic response a) | Mutant | Blindness; photoreceptor synaptic transmission defects | [133, 136] | Pyruvate Dehydrogenase Deficiency | — |
| dynactin 1a (dctn1a, mikre oko) | Mutant | Retinal degeneration | [123, 251] | — | — |
| dynactin 2 (p50), (dctn2, ale oko) | Mutant | Retinal degeneration | [120] | — | — |
| erythrocyte membrane protein band 4.1-like 5 (epb41l5, mosaic eyes) | Mutant | Photoreceptor defects | [111, 112] | — | |
| fleer (flr) | Mutant | Rod outer-segment defects | [129, 252] | — | — |
| intraflagellar transport proteins, 57, 80, 88, and 172 (ift57hi3417Tg, oval(ift88), ift172hi2211Tg) | Mutants (ift57, 88, 172), Morpholino (ift80) | Outer segment defects; retinal degeneration | [104, 126, 127, 253] | — | — |
| membrane protein, palmitoylated 5a (mpp5a, nagie oko) | Mutant | Disrupted RPE; retinal laminaiton defects; photoreceptor defects | [254, 255] | — | — |
| Novel protein (partial optokinetic response b) | Mutant | Cone degeneration | [256, 257] | — | — |
| phosphodiesterase 6 alpha (pde6α, eclipse) | Mutant | Cone degeneration | [258] | — | — |
| protein kinase C iota (prkci, heart and soul) | Mutant | Photoreceptor morphogenesis defects | [259] | — | — |
| protocadherin 15b (pcdh15b) | Morpholino | Photoreceptor defects; visual function defects | [260] | Usher Syndrome | 605514 |
| TNF receptor-associated factor 3 interacting protein (traf3ip, elipsa) | Mutant | Photoreceptor defects; visual defects | [128, 129] | — | — |
| Unknown (brudas) | Mutant | Photoreceptor defects | [129] | — | — |
| Unknown (niezerka) | Mutant | Photoreceptor defects | [129, 261] | — | — |
| Unknown (nightblindness a,b,e,f,g) | Mutant | Visual function defects; retinal degeneration (nba, nbe, nbf) | [137, 138, 141] | — | — |
| Other Retinal Phenotypes | |||||
| patched2 (ptc2, leprechaun) | Mutant | Müller glial reactivity; vitreo-retinal abnormalities | [165] | Basal Cell Naevus Syndrome (BCNS) | 601309 |
| phosphatase and tensin homolog b (ptenb) | Mutant | Ocular tumors | [262] | — | — |
| RPE | |||||
| choroideremia (chm) | Mutant | Retinal degeneration; RPE defects | [145, 146] | Choroideremia | 300390 |
| protein kinase C iota (prkci, heart and soul) | Mutant | RPE morphogenesis defects | [259] | — | — |
| silver homolog a (silva, fading vision) | Mutant | RPE defects; photoreceptor defects | [158] | — | — |
| vacuolar protein sorting 18p (vps18, vps18phi2499aTg) | Mutant | Melanosome maturation defects; reduced visual function | [149] | — | — |
| vacuolar protein sorting 39 homolog (vps39, leberknodel) | Mutant | RPE vesicle traffic defects; PR defects | [148] | — | — |
| v-ATPase complex (multiple genes) | Mutants | Melanosome defects; photoreceptor outer segment defects; | [153] | — | — |
| Unknown (bleached) | Mutant | Pigmentation defect; blindness; retinal degeneration | [155] | — | — |
| Unknown (fade out) | Mutant | RPE defects; photoreceptor defects | [156] | — | — |
| Unknown (gantenbein) | Mutant | Cone dystrophy; RPE degeneration | [154] | — | — |
| Hyaloid Vasculature | |||||
| forkhead box C1a (foxc1a) + forkhead box C1b (foxc1b) | Morpholino (coinjection) | reduced hyaloid basement membrane integrity | [186] | Axenfield-Reiger Syndrome, glaucoma | 601090 |
| heparan sulfate 6-O-sulfotransferase 2 (hs6st2) | Morpholino | aberrant patterning of hyaloid vasculature | [185] | — | — |
| laminin, α1 (lama1) | Morpholino | hyaloid vasculature dysmorphogenesis | [209] | — | — |
| laminin, α1 (lama1, bashful) | Mutant | no hyaloid vasculature | [185] | — | — |
| mab-21-like 2 (mab21l2) | Morpholino | reduced hyaloid vasculature | [185] | — | — |
| microfibrillar-associated protein 2 (mfap2) | Morpholino | reduced hyaloid vasculature branching | [185] | — | — |
| plexin D1 (plxnd1, out of bounds) | Mutant | aberrant patterning of hyaloid vasculature | [185] | — | — |
| syndecan 2 (sdc2) | Morpholino | no vasculature on the lens | [185] | — | — |
| Unknown (fused eyes) | Mutant | no hyaloid vasculature | [185] | — | — |
| Unknown (margin affected) | Mutant | reduced, then absent hyaloid vasculature | [185] | — | — |
| Unknown (platinum) | Mutant | premature detachment of hyaloid vasculature from lens | [185] | — | — |
| Lens | |||||
| cadherin 4, retinal (cdh4) | Morpholino | Small opaque lens | [263] | — | — |
| CDP-diacylglycerol-inositol 3-phosphatidyltransferase (cdipt, lens opaque) | Mutant | Lens cell hyperproliferation; lens degeneration | [264–266] | — | — |
| choroideremia (chm) | Mutant | Small opaque lens | [217] | Choroideremia | 300390 |
| coatomer protein complex, subunit ζ1 (copz1, copz1hi528Tg) | Mutant | Cortical lens defects | [104] | — | — |
| connexin 48.5 (cx48.5) | Morpholino | Cataracts and small lens | [267] | Cataracts | 121015 |
| decapentaplegic and Vg-related 1 (dvr1) | Morpholino | Retention of nuclei in lens fibers | [268] | — | — |
| fibroblast growth factor 19 (fgf19) | Morpholino | Defective lens cell survival and differentiation | [240, 269] | — | — |
| forkhead box E3 (foxe3) | Morpholino | Lens dysmorphogenesis; epithelial cell hyperproliferation; defective fiber differentiation | [202, 203] | Congenital primary aphakia, Peter's anomaly, Cataracts | 601094 |
| growth differentiation factor 6a (gdf6a) | Morpholino | Cortical lens defects; defective lens gene expression | [270, 271] | Microphthalmia | 601147 |
| heat shock cognate 70-kd protein (hsp70) | Morpholino | Immature lens | [272] | — | — |
| heat shock transcription factor 1 (hsf1) | Morpholino | Small lens | [273] | — | — |
| integrator complex subunit 7 (ints7, ints7hi1548Tg, ints7hi3649Tg) | Mutant | Devere lens disorganization | [104] | — | — |
| laminin, α1 (lama1) | Morpholino | Lens degeneration | [210] | — | — |
| laminin, α1 (lama1, bashful) | Mutant | Lens degeneration, focal corneal dysplasia | [209, 215, 216, 219, 264] | — | — |
| laminin, β1 (lamb1, grumpy, lamb1hi1113bTg) | Mutant | Cortical lens defects; lens dysplasia | [105, 217, 219] | — | — |
| laminin, γ1 (lamc1, sleepy, lamc1hi3890Tg) | Mutant | Cortical lens defects; lens dysplasia and degeneration | [104, 105, 219] | — | — |
| lengsin, lens protein with glutamine synthetase domain (lgsn) | Morpholino | Lens dysmorphogenesis; lens fiber defects | [274] | — | — |
| mab-21-like 2 (mab21l2) | Morpholino | Lens cell death | [275] | — | — |
| paired box gene 2a (pax2a, no isthmus) | Mutant | Small opaque lens by 6 dpf | [217] | Coloboma | 167409 |
| paired box gene 6b (pax6b) | Morpholino | Variable phenotype: small lens to absent lens | [276] | Peter's anomaly, Aniridia | 607108 |
| paired box gene 6b (pax6b, sunrise) | Mutant | Small lens | [277, 278] | Peter's anomaly, Aniridia | 607108 |
| paired-like homeodomain transcription factor 3 (pitx3) | Morpholino | Lens dysmorphogenesis: disordered epithelial cells, defective fiber differentiation, fiber cell death | [200–202] | Cataracts, Anterior segment dysgenesis | 602669 |
| patched 1 (ptc1) | Morpholino | Small, dysplastic lens | [84] | — | — |
| retinal homeobox gene 3 (rx3, chokh) | Mutant | Small lens, no retina | [279] | Anophthalmia/ Microphthalmia | 601881 |
| RNA binding motif 42 (rbm42, rbm42hi2735ATg) | Mutant | Cortical lens defects | [104] | — | — |
| syndecan 2 (sdc2) | Morpholino | Small lens | [185] | — | — |
| ubiquitin-like, containing PHD and RING finger domains, 1 (uhrf1, uhrf1hi272Tg, uhrf1hi3020Tg) | Mutant | Lens disorganization and degeneration | [104] | — | — |
| WD repeat domain 36 (wdr36, wdr36hi3630aTg) | Mutant | Thickening of lens epithelium; cortical lens defects; lens degeneration | [280] | Primary open-angle glaucoma | 609669 |
| Unknown (bumper) | Mutant | Lens epithelial cell hyperproliferation, lens fiber degeneration | [135, 278, 281] | — | — |
| Unknown (chiorny) | Mutant | Small lens | [282] | — | — |
| Unknown (cloche) | Mutant | Opaque lens with retained nuclei | [205] | — | — |
| Unknown (disrupted lens) | Mutant | Disorganized lens fibers | [215, 264] | — | — |
| Unknown (dou yan) | Mutant | Small lens | [283] | — | — |
| Unknown (korinthe) | Mutant | Lens degeneration | [278] | — | — |
| Unknown (margin affected) | Mutant | Small lens | [185] | — | — |
| Unknown (platinum) | Mutant | Small lens | [185] | — | — |
| Unknown (rosine) | Mutant | Lens degeneration | [278] | — | — |
| Unknown (yol) | Mutant | Lens degeneration | [164] | — | — |
*
Online Mendelian Inheritance in Man (OMIM) entries are listed if the disrupted zebrafish gene is orthologous to a human gene associated with an ocular disease.