title: Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development.
abstract: To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500 different genes--roughly 20% of the genes that can be mutated to produce a visible embryonic phenotype in this species--and will clone the majority of the mutated alleles. So far, we have isolated more than 500 insertional mutants. Here we describe the first 75 insertional mutants for which the disrupted genes have been identified. In agreement with chemical mutagenesis screens, approximately one-third of the mutants have developmental defects that affect primarily one or a small number of organs, body shape or swimming behavior; the rest of the mutants show more widespread or pleiotropic abnormalities. Many of the genes we identified have not been previously assigned a biological role in vivo. Roughly 20% of the mutants result from lesions in genes for which the biochemical and cellular function of the proteins they encode cannot be deduced with confidence, if at all, from their predicted amino-acid sequences. All of the genes have either orthologs or clearly related genes in human. These results provide an unbiased view of the genetic construction kit for a vertebrate embryo, reveal the diversity of genes required for vertebrate development and suggest that hundreds of genes of unknown biochemical function essential for vertebrate development have yet to be identified.
authors: Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors: Gregory
authors: G
authors: Golling
authors: Adam
authors: A
authors: Amsterdam
authors: Zhaoxia
authors: Z
authors: Sun
authors: Marcelo
authors: M
authors: Antonelli
authors: Ernesto
authors: E
authors: Maldonado
authors: Wenbiao
authors: W
authors: Chen
authors: Shawn
authors: S
authors: Burgess
authors: Maryann
authors: M
authors: Haldi
authors: Karen
authors: K
authors: Artzt
authors: Sarah
authors: S
authors: Farrington
authors: Shuh-Yow
authors: SY
authors: Lin
authors: Robert M
authors: RM
authors: Nissen
authors: Nancy
authors: N
authors: Hopkins
mesh_terms: D000818:Animals; D003001:Cloning, Molecular / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009154:Mutation; D012190:Retroviridae / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*