Histology-based screen for zebrafish mutants with abnormal cell differentiation

被引:25
作者
Mohideen, MAPK
Beckwith, LG
Tsao-Wu, GS
Moore, JL
Wong, ACC
Chinoy, MR
Cheng, KC
机构
[1] Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst H059, Dept Pathol, Hershey, PA 17033 USA
[2] Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Dept Surg, Hershey, PA 17033 USA
[3] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[4] Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Dept Biochem & Mol Biol, Hershey, PA 17033 USA
关键词
zebrafish mutant; larval arrays; histology; cell differentiation; retina; cancer;
D O I
10.1002/dvdy.10407
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:414 / 423
页数:10
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