Four specific aims are outlined, and a fifth is proposed if time permits.
Each specific aim i s directed toward the primary goal of producing genetically altered mice that can serve as a model for the detection of mutagenic compounds. Rather than use bacterial genes, as current models of transgenic mutagenesis use, the candidate proposes to use the ubiquitously active endogenous gene, adenosine phosphoribosyl transferase (APRT), at its resident locus as a reporter. The first four specific aims will characterize and evaluate mutations of Aprt in embryonic stem (ES) cells. The fifth specific aim, which will be performed if time permits, will examine reversion frequencies in mice carrying mutant, revertible Aprt alleles. This proposal should be excellent training for the candidate. It is very well prepared and should produce useful results, especially if specific aim 5 is addressed. The proposal is ambitious and does not get to an in vivo model until specific aim 5, if at all, even though the candidate indicates that this proposal will overcome current limitations of the vivo models. Nevertheless, this is an excellent to outstanding proposal overall.
