RT Journal Article
SR Electronic
T1 Genetic Disorders of Vision Revealed by a Behavioral Screen of 400 Essential Loci in Zebrafish
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8603
OP 8615
DO 10.1523/JNEUROSCI.19-19-08603.1999
VO 19
IS 19
A1 Stephan C. F. Neuhauss
A1 Oliver Biehlmaier
A1 Mathias W. Seeliger
A1 Tilak Das
A1 Konrad Kohler
A1 William A. Harris
A1 Herwig Baier
YR 1999
UL http://www.jneurosci.org/content/19/19/8603.abstract
AB We examined optokinetic and optomotor responses of 450 zebrafish mutants, which were isolated previously based on defects in organ formation, tissue patterning, pigmentation, axon guidance, or other visible phenotypes. These strains carry single point mutations in >400 essential loci. We asked which fraction of the mutants develop blindness or other types of impairments specific to the visual system. Twelve mutants failed to respond in either one or both of our assays. Subsequent histological and electroretinographic analysis revealed unique deficits at various stages of the visual pathway, including lens degeneration (bumper), melanin deficiency (sandy), lack of ganglion cells (lakritz), ipsilateral misrouting of axons (belladonna), optic-nerve disorganization (grumpy and sleepy), inner nuclear layer or outer plexiform layer malfunction (noir,dropje, and possibly steifftier), and disruption of retinotectal impulse activity (macho andblumenkohl). Surprisingly, mutants with abnormally large or small eyes or severe wiring defects frequently exhibit no discernible behavioral deficits. In addition, we identified 13 blind mutants that display outer-retina dystrophy, making this syndrome the single-most common cause of inherited blindness in zebrafish. Our screen showed that a significant fraction (∼5%) of the essential loci also participate in visual functions but did not reveal any systematic genetic linkage to particular morphological traits. The mutations uncovered by our behavioral assays provide distinct entry points for the study of visual pathways and set the stage for a genetic dissection of vertebrate vision.