Our laboratory investigates mechanisms of gene control in the living mammalian organism. Specific genes are introduced by microinjection into the germ line of mice, and expression of these genes is assayed in the resulting transgenic animals. To this end, organ screens are performed at various stages of development from fetus to adult. Two problems were studied. The first dealt with oncogenesis in the transgenic animal. A fused gene, consisting of the mouse Alpha crystallin promoter and the coding sequences of the SV40 tumor antigens, was inserted in the mouse germ line. Lens tumors developed in all mouse lines generated so far. Tumor cells expressed the SV40 T antigen. The onset of cell transformation coincided with lens differentiation during mid-getation. The second problem concerns insertional mutagenesis observed in one of our strains of transgenic mice. A dominant phenotype of small litter size was shown to coincide with a chromosome 6/17 reciprocal translocation, and the gene insert was localized by in situ hybridization to one of the rearranged chromosomes.

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
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Country
United States
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Gorivodsky, Marat; Mukhopadhyay, Mahua; Wilsch-Braeuninger, Michaela et al. (2009) Intraflagellar transport protein 172 is essential for primary cilia formation and plays a vital role in patterning the mammalian brain. Dev Biol 325:24-32
Storbeck, Chris J; Wagner, Simona; O'Reilly, Paul et al. (2009) The Ldb1 and Ldb2 transcriptional cofactors interact with the Ste20-like kinase SLK and regulate cell migration. Mol Biol Cell 20:4174-82
Backman, Cristina M; Zhang, YaJun; Malik, Nasir et al. (2009) Generalized tetracycline induced Cre recombinase expression through the ROSA26 locus of recombinant mice. J Neurosci Methods 176:16-23
Lewis, Samara L; Khoo, Poh-Lynn; De Young, R Andrea et al. (2008) Dkk1 and Wnt3 interact to control head morphogenesis in the mouse. Development 135:1791-801
Zhao, Yangu; Flandin, Pierre; Long, Jason E et al. (2008) Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. J Comp Neurol 510:79-99
Hwang, Minyoung; Gorivodsky, Marat; Kim, Minjung et al. (2008) The neuronal differentiation potential of Ldb1-null mutant embryonic stem cells is dependent on extrinsic influences. Stem Cells 26:1490-5
Ellwanger, Kristina; Saito, Hiroaki; Clement-Lacroix, Philippe et al. (2008) Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Mol Cell Biol 28:4875-82
Cheung, Yuk Yin; Kim, So Youn; Yiu, Wai Han et al. (2007) Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta. J Clin Invest 117:784-93
Lewis, Samara L; Khoo, Poh-Lynn; Andrea De Young, R et al. (2007) Genetic interaction of Gsc and Dkk1 in head morphogenesis of the mouse. Mech Dev 124:157-165
Suleiman, Hani; Heudobler, Daniel; Raschta, Anne-Sarah et al. (2007) The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev Biol 304:701-12

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