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Title: A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines

item Boles, Melissa
item Wilkinson, Bonney
item Maxwell, Andrea
item Lai, Lihua
item Mills, Alea
item Nishijima, Ichiko
item Salinger, Andrew
item Moskowitz, Ivan
item Hirschi, Karen
item Liu, Bin
item Bradley, Allan
item Justice, Monica

Submitted to: BioMed Central (BMC) Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/6/2009
Publication Date: 3/6/2009
Citation: Boles, M.K., Wilkinson, B.M., Maxwell, A., Lai, L., Mills, A.A., Nishijima, I., Salinger, A.P., Moskowitz, I., Hirschi, K.K., Liu, B., Bradley, A., Justice, M.J. 2009. A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines. Biomed Central (BMC) Genetics. 10:12.

Interpretive Summary: These studies were done to identify the gene mutation among many mouse mutants that were created using ENU, a chemical mutagen. Some of the resulting mutant mouse lines are being analyzed for defects in cardiovascular development.

Technical Abstract: ENU-mutagenesis is a powerful technique to identify genes regulating mammalian development. To functionally annotate the distal region of mouse chromosome 4, we performed an ENU-mutagenesis screen using a balancer chromosome targeted to this region of the genome. We isolated 11 lethal lines that map to the region of chromosome 4 between D4Mit117 and D4Mit281. These lines form 10 complementation groups. The majority of lines die during embryonic development between E5.5 and E12.5 and display defects in gastrulation, cardiac development, and craniofacial development. One line displayed postnatal lethality and neurological defects, including ataxia and seizures. These eleven mutants allow us to query gene function within the distal region of mouse chromosome 4 and demonstrate that new mouse models of mammalian developmental defects can easily and quickly be generated and mapped with the use of ENU-mutagenesis in combination with balancer chromosomes. The low number of mutations isolated in this screen compared with other balancer chromosome screens indicates that the functions of genes in different regions of the genome vary widely.