Histology-based screen for zebrafish mutants with abnormal cell differentiation.
Journal
  Developmental dynamics : an official publication of the American Association of Anatomists.
Citation
  Dev Dyn. 228(3):414-23
Publication date
  2003 Nov
Authors
  Mohideen MA
Beckwith LG
Tsao-Wu GS
Moore JL
Wong AC
Chinoy MR
Cheng KC
Investigators
  Keith C. Cheng
Mala R. Chinoy
Grant agencies
  National Institute of General Medical Sciences
National Cancer Institute
National Institute of Child Health and Human Development
Grants
  NIGMS IF32GM19794
NCI R01-CA73935
NICHD R01-HD040179
MeSH headings
  Cell Differentiation
Mutagenesis
Zebrafish
MeSH qualifiers
  genetics
Abstract
  The power of histology to define states of cell differentiation was used as the basis of a mutagenesis screen in zebrafish. In this screen, 7-day-old parthenogenetic half-tetrad larvae from potential carrier females were screened for mutations affecting cell differentiation in hematoxylin and eosin-stained tissue sections. Seven, noncomplementing, recessive mutations were found. Two mutations affect only the retina: segmented photoreceptors (spr) show a discontinuous photoreceptor cell layer; vestigial outer segments (vos) has fewer photoreceptor cells and degenerated outer segments within this cell layer. Three mutants have gut-specific defects: the epithelial cells of kirby (kby) are replaced by ballooned cells; the intestines of stuffy (sfy) and stuffed (sfd) contain increased luminal mucus. Two mutations affect multiple organs: disordered neural retina (dnr) has disrupted retinal layering and mild nuclear abnormalities in the gut and liver; and in huli hutu (hht), the retinal cell layers are disorganized and multiple organs have mild to severe nuclear abnormalities that are reminiscent of the atypia of human neoplasia. Each mutation appears to be homozygous lethal. This screen is proof of principle for the feasibility of histologic screens to yield novel mutations, including potential models of human disease. The throughput for this type of screen may be enhanced by automation.
Medline ID
  22939562