Zebrafish mutants: Behavioral genetic studies of visual system defects

Abstract

Zebrafish are a promising model for behavioral and genetic studies of vertebrate visual system development and retinal degeneration. In the past few years, numerous studies on zebrafish vision have been published. While most of the studies focus on the molecular and cellular characterization of mutations that disrupt zebrafish visual system structure in early development, others examine the mechanisms that underlie inherited visual system disorders in adults. Behavioral assays, along with morphologic and electrophysiological methods, are powerful tools for functional analyses of zebrafish visual development and performance.

Isolation and characterization of the laure olfactory behavioral mutant in the zebrafish, Danio rerio

“…In Drosophila, for example, adult flies bearing the optomotor blind (omb) mutant allele, omb H31 , show an impaired optomotor behavioral response; yet, more severe mutant alleles are lethal (Pflugfelder and Heisenberg, 1995). Likewise, in zebrafish, a behavioral screen based on the fish's escape response was used to isolate the night blind a (nba) mutation (Li and Dowling, 1997;Li, 2001). Interestingly, nba heterozygotes show degeneration that is restricted to the retina, whereas homozygotes die as embryos, show degeneration throughout the CNS, as well as abnormalities in other organs such as the heart (Li, 2001;Maaswinkel et al, 2003), indicating that nba has functions outside of the retina.…”

“…Likewise, in zebrafish, a behavioral screen based on the fish's escape response was used to isolate the night blind a (nba) mutation (Li and Dowling, 1997;Li, 2001). Interestingly, nba heterozygotes show degeneration that is restricted to the retina, whereas homozygotes die as embryos, show degeneration throughout the CNS, as well as abnormalities in other organs such as the heart (Li, 2001;Maaswinkel et al, 2003), indicating that nba has functions outside of the retina. Future isolation of additional lre alleles, and mapping and molecular identification of the lre gene will aid in resolving these important questions.…”

Zebrafish mutants as models for congenital ocular disorders in humans

“…Zebrafish also do not possess iris muscles, instead, the zebrafish iris contains several types of pigment cells that may function in preventing light from entering the eye outside of the pupil (Soules and Link, 2005). Nonetheless, there is Karlstrom et al (1996) brudas (bru) Unknown -Photoreceptor defects Malicki et al (1996) cloche (clo) Cataracts Goishi et al (2006) elipsa (eli) Unknown -Photoreceptor defects Malicki et al (1996) fade out (fad) Unknown -RPE/retinal degeneration Bahadori et al (2006) fading vision (fdv) silva 193500 RPE pigmentation, visual function (embryonic) Schonthaler et al (2005) fleer (flr) Unknown -Photoreceptor defects Malicki et al (1996) gantenbein ( mikre oko (mok) Unknown -Photoreceptor defects Malicki et al (1996) n-cadherin (ncad) ncad -Coloboma, retinal disorganization Masai et al (2003); Erdmann et al (2003); Malicki et al (2003) niezerka (nie) Unknown -Photoreceptor defects Malicki et al (1996) Night blindness (nba, nbb, nbc, nbd, nbe, nbf, nbg) Unknown -Night blindness (heterozygotes) Li andDowling (1997, 2000); Maaswinkel et al (Maaswinkel et al, 2003a(Maaswinkel et al, ,b, 2005 no optokinetic response a (noa) dlat 245348 Visual function Taylor et al (2004) no optokinetic response f (nof) gnat2 139340 Visual function …”

“…To identify dominant mutations affecting visual function, Li and co-workers successfully utilized an escape response behavioral assay to measure visual thresholds in adult animals (Li, 2001). This test is performed on the F1 generation fish following ENU mutagenesis to detect night blindness beginning as early at 2-3 months of age.…”

“…Night blindness can result from nondegenerative diseases (i.e., congenital stationary night blindness) or degenerative diseases such as retinitis pigmentosa. Screens utilizing the escape response assay have identified seven night blindness loci (nba, nbb, nbc, nbd, nbe, nbf, nbg) (Li andDowling, 1997, 2000;Maaswinkel et al, 2003aMaaswinkel et al, ,b, 2005. Six of the seven heterozygous mutants (all but nbb) exhibit some degree of photoreceptor degeneration; however, the degree of degeneration varies dramatically between mutants.…”