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

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

doi:10.1186/1471-2156-10-12

Abstract

BackgroundENU-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.ResultsWe 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.ConclusionThese 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.

Highlights

ENU-mutagenesis is a powerful technique to identify genes regulating mammalian development
Chromosome 4 balancer screen We report here the use of a mouse chromosome 4 balancer in an ENU-mutagenesis screen
Our ability to genotype throughout development and after birth by eye pigment, coat color, or PCR provided a great advantage over traditional mutagenesis screens in determining if phenotypes segregated to the balancer region

Summary

Introduction

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. In order to examine gene function in targeted regions of the genome, we have taken an approach to mutagenesis screening that does not bias the results towards a particular developmental stage or defect. We previously reported 78 recessive novel lethal mutants that die before three weeks of age (59 were mapped to chromosome 11 and 19 were mapped to chromosome 4) [4,5]. These chromosomes were targeted because of their high conservation with human chromosomes 17 and 1, respectively. By targeting a region with high human conservation, we sought to functionally annotate the genes in the region, and create mouse models of human diseases that map to the corresponding region of human chromosome 1

Methods

Results

Discussion

Conclusion