Open Access Research article

High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5

Yung-Hao Ching1, Robert J Munroe1, Jennifer L Moran2, Anna K Barker1, Evan Mauceli2, Tim Fennell2, Frederica diPalma2, Kerstin Lindblad-Toh24, Lindsay M Abcunas1, Joyanna F Gilmour3, Tanya P Harris1, Susan L Kloet1, Yunhai Luo1, John L McElwee1, Weipeng Mu1, Hyo K Park1, David L Rogal1, Kerry J Schimenti1, Lishuang Shen1, Mami Shindo1, James Y Shou1, Erin K Stenson1, Patrick J Stover3 and John C Schimenti1*

Author Affiliations

1 Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA

2 The Broad Institute, Seven Cambridge Center, Cambridge, MA 02142, USA

3 Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA

4 Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden

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BMC Genetics 2010, 11:106  doi:10.1186/1471-2156-11-106

Published: 30 November 2010



Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a ~50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals.


We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis.


This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.