In Vivo Models of NF-1: The Nervous System and Tumorigenesis.
Annual rept. 1 Sep 97-31 Aug 98,
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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It is believed that the primary function of the protein encoded by the NF-1 gene is as a negative regulator of the ras protooncogene. Mutation of the NF-1 gene therefore releases ras function from negative regulation leading to hyperplasia and defects in multiple neural crest derived tissues. We have embarked on the generation of conditional mutant mice at the NF-1 locus and at the ras-Gap locus since these two genes are thought to be the major negative modulators of ras activity. In the first year Objectives 1 and 2, we have confirmed germline transmission and activity of the NF-1 conditional allele. In addition we have embarked on various cellular and cre-transgenic mediated strategies to further study NF-1 function as proposed. In addition, as outlined in Objective 2, we have constructed a conditional ras-gap allele, introduced it into ES cells, and generated chimeric mice for the propagation of conditional mutant mice. Thus we have achieved all of our proposed goals for the first year and plan to continue along the outlined strategies in year 2.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology