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absent. Cones were almost completely absent by 12 wpf and the number of neurons in all layers of the retina
were decreased. Rods continued to be maintained, although rhodopsin staining was reduced compared to
wild-type siblings. Interestingly, proliferation of rod precursors in the ONL of gosh mutants was observed
[61]
beginning at 5 wpf . There was also a small increase in the number of proliferating Müller glia in the INL
of gosh mutants. Subsequent genetic mapping of the gosh locus identified an aipl1 gene as a candidate for
the gosh mutant. Sequencing of this gene uncovered a nonsense mutation. The zebrafish genome contain
two aipl1 orthologs, aipl1a and aipl1b. The aipl1a gene is more similar to human AIPL1. The gosh mutant
was caused by a mutation in the aipl1b gene. Expression of aipl1b was restricted to cones, whereas aipl1a
was expressed in rods and likely UV cones. The cone-specific expression of aipl1b likely explains why cones
degenerated in gosh mutants. Cones degenerated rapidly in gosh mutants but rods also begin degenerating
[61]
by 3 weeks post fertilization, indicating that aipl1b is necessary for both cone and rod survival . A follow-
up study found that the rapid degeneration of cones triggered a modest proliferation of Müller glia and rod
degeneration resulted in proliferation of rod precursors. Within the INL, the proliferating Müller glia
expressed Sox2 and the neural progenitors expressed Pax6. Individual Pax6+ cells appeared to migrate to the
ONL. Given that the proliferating Müller glia did not result in cone regeneration, it is possible that the
Pax6+ neural precursors were rod progenitors en route to the ONL to provide additional rod precursors and
attempt to regenerate rods .
[62]

BBS2
BBS is clinically and genetically heterogeneous autosomal recessive disorder characterized by retinal
degeneration, obesity, renal dysfunction, polydactyly, and mental retardation [63,64] . To date, mutations in 22
genes have been shown to cause BBS . BBS2 encodes a core protein of the BBSome , which is an
[65]
[66]
octomeric protein complex required for protein trafficking through the photoreceptor cilium [67,68] . The
bbs2 mutant was generated by CRISPR/Cas9 mutagenesis and exhibited impaired OKR responses and
lri82
[69]
shortened cone outer segments at 5 dpf . The bbs2 mutants lived into adulthood, but were smaller and
exhibited spinal curvatures that are consistent with ciliopathy phenotypes in zebrafish . In adult bbs2
[70]
mutants, cone photoreceptors degenerated and rods exhibiting rhodopsin mislocalization. A significant
increase in proliferating cells within the outer nuclear layer of adult bbs2 mutants suggested that rods were
being regenerated from rod precursors. No proliferation of Müller glia was observed in bbs2 mutants,
indicating that the regeneration typically seen following acute injury did not occur. The lack of Müller glia
proliferation was not due to the bbs2 mutation, as acute light injury was capable of triggering a regeneration
response in both bbs2 mutants and wild-type siblings.

Centrosomal protein 290-kD
The centrosomal protein 290-kD gene (CEP290) encodes a large, multidomain coiled-coil protein that
localizes to the ciliary TZ and to the centrosome/basal body in motile and non-motile cilia [71-73] . As a
component of the TZ, Cep290 regulates protein trafficking through the cilium and facilitates ciliary
[74]
assembly [75,76] . In humans, more than 130 mutations in CEP290 have been shown to cause a variety of
ciliopathy disorders, including JBTS, BBS, Senior-Loken syndrome, Meckle syndrome, and
nephronophthisis [77,78] , with retinal dystrophy being a common symptom. Mutations in CEP290 can also
result in non-syndromic retinal degenerations such as early-onset LCA and late-onset RP . Despite
[79]
[80]
several years of intense study on CEP290 genetics in humans and in animal models, no consensus exists to
explain CEP290 pleiotropy or to establish genotype-phenotype correlations. Three distinct zebrafish cep290
mutant lines have been described in the literature. The cep290 fh297 allele is a nonsense point mutation
(p.Gln1217X) that was induced by ethynitrosourea (ENU) . The cep290 fh297 mutant had normal visual
[81]
function by OKR assays and normal photoreceptor structure at 5 dpf . The cep290 fh378 mutant allele was
[81]
made using TALEN genome editing and resulted in a 2 bp deletion that produces a downstream stop codon