Abstract

Gene targeting provides the means for creating strains of mice with mutations in virtually any gene. This technology permits evaluation of the function of genes in an intact mouse and the systematic dissection of the most complex of biological processes, including the study of cancer, immunology and neurobiology. In this grant we are seeking to extend the gene targeting technology beyond its common use to generate """"""""knockout"""""""" mice. Emphasis will be placed on improving conditional mutagenesis protocols by incorporating, for example, Cre-based and FIp-based self-excision cassettes to allow more rapid removal of unwanted DNA sequences when the cassette passes through the male germ line. We also propose to generate a Cre-loxP-based conditional mutagenesis system that can be modulated temporally. Such extensions should improve the gene targeting technology and make it more useful for the generation of mouse models of human genetic disease and the study of human medicine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021168-32
Application #
6984093
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Haynes, Susan R
Project Start
1976-12-01
Project End
2007-08-04
Budget Start
2005-12-01
Budget End
2007-08-04
Support Year
32
Fiscal Year
2006
Total Cost
$385,098
Indirect Cost

  Institution

Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Du, Xuguang; Feng, Tao; Yu, Dawei et al. (2015) Barriers for Deriving Transgene-Free Pig iPS Cells with Episomal Vectors. Stem Cells 33:3228-38
Haldar, Malay; Karan, Goutam; Watanabe, Shuichi et al. (2014) Response: Contributions of the Myf5-independent lineage to myogenesis. Dev Cell 31:539-41
Straessler, Krystal M; Jones, Kevin B; Hu, Hao et al. (2013) Modeling clear cell sarcomagenesis in the mouse: cell of origin differentiation state impacts tumor characteristics. Cancer Cell 23:215-27
Jones, Kevin B; Datar, Manasi; Ravichandran, Sandhya et al. (2013) Toward an understanding of the short bone phenotype associated with multiple osteochondromas. J Orthop Res 31:651-7
Jones, K B; Su, L; Jin, H et al. (2013) SS18-SSX2 and the mitochondrial apoptosis pathway in mouse and human synovial sarcomas. Oncogene 32:2365-71, 2375.e1-5
Su, Le; Sampaio, Arthur V; Jones, Kevin B et al. (2012) Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics. Cancer Cell 21:333-47
Makki, Nadja; Capecchi, Mario R (2012) Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum Mol Genet 21:26-31
Yan, Kelley S; Chia, Luis A; Li, Xingnan et al. (2012) The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci U S A 109:466-71
Rogers, Scott W; Tvrdik, Petr; Capecchi, Mario R et al. (2012) Prenatal ablation of nicotinic receptor alpha7 cell lineages produces lumbosacral spina bifida the severity of which is modified by choline and nicotine exposure. Am J Med Genet A 158A:1135-44
Boulet, Anne M; Capecchi, Mario R (2012) Signaling by FGF4 and FGF8 is required for axial elongation of the mouse embryo. Dev Biol 371:235-45

Showing the most recent 10 out of 18 publications