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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Yung-Hao Ching, Robert J Munroe, Jennifer L Moran, Anna K Barker, Evan Mauceli, Tim Fennell, Frederica diPalma, Kerstin Lindblad-Toh, Lindsay M Abcunas, Joyanna F Gilmour, Tanya P Harris, Susan L Kloet, Yunhai Luo, John L McElwee, Weipeng Mu, Hyo K Park, David L Rogal, Kerry J Schimenti, Lishuang Shen, Mami Shindo, James Y Shou, Erin K Stenson, Patrick J Stover, John C Schimenti

ABSTRACT

BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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. More... »

PAGES

106

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2156-11-106

DOI

http://dx.doi.org/10.1186/1471-2156-11-106

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038531290

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21118569


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