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Open Access Highly Accessed Research article

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

Melissa K Boles12, Bonney M Wilkinson1, Andrea Maxwell1, Lihua Lai6, Alea A Mills3, Ichiko Nishijima4, Andrew P Salinger1, Ivan Moskowitz5, Karen K Hirschi6, Bin Liu1, Allan Bradley7 and Monica J Justice12*

Author Affiliations

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA

2 Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA

3 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

4 Center for Molecular and Human Genetics, Columbus Children's Research Institute, The Ohio State University, Columbus, OH 43205, USA

5 Departments of Pediatrics and Pathology, Institute for Molecular Pediatric Sciences, The University of Chicago, Chicago, IL 60637, USA

6 Departments of Pediatrics and of Molecular and Cellular Biology, Center for Cell and Gene Therapy, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA

7 Wellcome Trust Sanger Institute, Hinxton, UK

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BMC Genetics 2009, 10:12  doi:10.1186/1471-2156-10-12

Published: 6 March 2009

Abstract

Background

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.

Results

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.

Conclusion

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.