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Open Access Research

An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse

Lucia Daxinger12, Sarah K Harten1, Harald Oey12, Trevor Epp16, Luke Isbel12, Edward Huang1, Nadia Whitelaw1, Anwyn Apedaile1, Anabel Sorolla1, Joan Yong1, Vandhana Bharti1, Joanne Sutton1, Alyson Ashe17, Zhenyi Pang1, Nathan Wallace1, Daniel J Gerhardt3, Marnie E Blewitt45, Jeffrey A Jeddeloh3 and Emma Whitelaw12*

Author Affiliations

1 Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Qld 4006, Australia

2 La Trobe Institute for Molecular Science, Department of Genetics, La Trobe University, Bundoora 3086, Vic, Australia

3 Development and Research, Roche NimbleGen, 500 South Rosa Road, Madison, WI 53705, USA

4 Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Melbourne 3050, Vic, Australia

5 Department of Medical Biology and Dept of Genetics, University of Melbourne, Melbourne 3050, Vic, Australia

6 Present address: Institute of Molecular Genetics of ASCR, Videnska 1083, Prague 4, Czech Republic

7 Present address: Gurdon Institute, University of Cambridge, Cambridge CB2 IQN, UK

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Genome Biology 2013, 14:R96  doi:10.1186/gb-2013-14-9-r96

Published: 11 September 2013

Abstract

Background

We have used a sensitized ENU mutagenesis screen to produce mouse lines that carry mutations in genes required for epigenetic regulation. We call these lines Modifiers of murine metastable epialleles (Mommes).

Results

We report a basic molecular and phenotypic characterization for twenty of the Momme mouse lines, and in each case we also identify the causative mutation. Three of the lines carry a mutation in a novel epigenetic modifier, Rearranged L-myc fusion (Rlf), and one gene, Rap-interacting factor 1 (Rif1), has not previously been reported to be involved in transcriptional regulation in mammals. Many of the other lines are novel alleles of known epigenetic regulators. For two genes, Rlf and Widely-interspaced zinc finger (Wiz), we describe the first mouse mutants. All of the Momme mutants show some degree of homozygous embryonic lethality, emphasizing the importance of epigenetic processes. The penetrance of lethality is incomplete in a number of cases. Similarly, abnormalities in phenotype seen in the heterozygous individuals of some lines occur with incomplete penetrance.

Conclusions

Recent advances in sequencing enhance the power of sensitized mutagenesis screens to identify the function of previously uncharacterized factors and to discover additional functions for previously characterized proteins. The observation of incomplete penetrance of phenotypes in these inbred mutant mice, at various stages of development, is of interest. Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines.