Elsevier

Gene Expression Patterns

Volume 6, Issue 6, August 2006, Pages 653-665
Gene Expression Patterns

Novel lethal mouse mutants produced in balancer chromosome screens

https://doi.org/10.1016/j.modgep.2005.11.015Get rights and content

Abstract

Mutagenesis screens are a valuable method to identify genes that are required for normal development. Previous mouse mutagenesis screens for lethal mutations were targeted at specific time points or for developmental processes. Here we present the results of lethal mutant isolation from two mutagenesis screens that use balancer chromosomes. One screen was localized to mouse chromosome 4, between the STS markers D4Mit281 and D4Mit51. The second screen covered the region between Trp53 and Wnt3 on mouse chromosome 11. These screens identified all lethal mutations in the balancer regions, without bias towards any phenotype or stage of death. We have isolated 19 lethal lines on mouse chromosome 4, and 59 lethal lines on chromosome 11, many of which are distinct from previous mutants that map to these regions of the genome. We have characterized the mutant lines to determine the time of death, and performed a pair-wise complementation cross to determine if the mutations are allelic. Our data suggest that the majority of mouse lethal mutations die during mid-gestation, after uterine implantation, with a variety of defects in gastrulation, heart, neural tube, vascular, or placental development. This initial group of mutants provides a functional annotation of mouse chromosomes 4 and 11, and indicates that many novel developmental phenotypes can be quickly isolated in defined genomic intervals through balancer chromosome mutagenesis screens.

Section snippets

Results and discussion

Mutagenesis screens have been used in the mouse since the 1950s. Originally, screens were performed to determine the efficacy of radiation at inducing mutations in seven visible loci – called the “Specific Locus Test” (SLT) (reviewed in Davis and Justice, 1998). Using the SLT, the chemical ENU was identified as a potent mutagen to induce point mutations in spermatogonial stem cells (Hitotsumachi et al., 1985). ENU screens have been used to identify recessive developmental defects in haploid

Mutagenesis screens

The design of the balancer chromosomes and the mutagenesis screens have been described in detail (Zheng et al., 1999, Kile et al., 2003, Hentges and Justice, 2004, Nishijima et al., 2003). For chromosome 4, we classified a line as lethal if no tester animals were recovered in a cohort of 30 carriers or homozygous balancer mice. For chromosome 11, we classified a line as lethal if no tester animals were recovered from that line at weaning in a cohort of 24 carriers. Lines where tester animals

Acknowledgements

The authors thank Colleen Viator and Maritess Alviento for superb technical assistance. This research was funded by U01 HD39372 to M.J.J. and F32 HD42436 to K.E.H.

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