Courses and Office Hours
My research interests concern the genetic analysis of development in mammals, using mice and rats as model mammalian systems. With the long-term goal of gaining access to the molecular biology underlying interesting mutant phenotypes, my work prior to my appointment at CCSU produced a number of high-resolution genetic maps including genomic regions on mouse Chromosomes 7, 10, 17 and the Y Chromosome. At CCSU, my laboratory has made progress pursuing five different projects:
1. We are investigating the molecular genetic basis of a pleiotropic developmental mutation in the mouse, designated mshi. This mutation involves recessive male sterility, and loss of an unusual new type of histocompatibility locus that is detected in vivo by helper T cells. We have recently mapped this mutation to mouse Chr 10 (Turner et al., Genomics 39, 1-7; Rule et al., Mammalian Genome 10, 447-450), and have made progress characterizing both the histocompatibility (Hildebrandt et al., Immunogenetics 49, 666-672) and reproductive aspects of the mutant phenotype. We are currently investigating the extent of programmed cell death (apoptosis) in mutant gonads, vs. wild type (in collaboration with James Mulrooney, CCSU); and are testing Esr1 as a likely candidate for the gene disrupted by the mshi mutation.
2. We are initiating a phenotypic and genetic characterization of a hairless mutant (called “shorn”) that arose spontaneously in CCSU’s laboratory rat colony. We have fine-mapped this mutation (shn) to rat Chr 7 (Moemeka et al., J. Heredity 89, 257-260; Hall et al., J. Heredity 91, 345-347), as a foundation for positional cloning of the shn gene. We plan also to investigate the involvement of compelling candidate gene families from the region where the mutation maps, including Hoxc, keratin type II, and aquaporins 2 and 5 (in collaboration with J. Mulrooney, R. Rollin, and K. Martin-Troy, CCSU). The observation of recombination suppression in the region of the mutation may suggest that a chromosomal inversion is the underlying cause of the complex phenotype, which includes, in addition to alopecia, defects in kidney function as well as maternal reproduction (Chrissluis et al., 2002, Molecular Genetics and Metabolism, 76, 335-339).
3. Another project, the mapping of the Charles River “hairless” mutation, was started and completed in Fall, 2001 (Ahearn et al., 2002,J. Heredity 93, 210-213). This work has suggested Fgfr2 as a possible gene candidate for the Charles River “hairless” mutation, which we also showed is an allele of rat fuzzy and a likely orthologue of mouse frizzy.
4. We are now intensively pursuing a series of experiments aimed at identifying any minor histocompatibility loci on the mouse X chromosome that might differ between standard inbred mouse strains. One such locus has been identified, called H-hixb, and we may have restricted its map location to a portion of the mouse X, and identified a second gene required for H-hixb antigen presentation (Alner et al., in press Immunogenetics). Our long-term goal is to identify and map other H-hix loci, if such differences exist between standard inbred mouse strains. This work is currently supported by an NIH AREA grant (through 2004).
5. We are currently piloting a new investigation to identify the first pseudoautosomal marker(s) in the rat. This project will make use of the two large DNA panels we have made for mapping the Charles River “hairless” mutation, and the rat shorn mutation. Preliminary data currently being collected will be used to support a new AREA grant application requesting support for this project, the submission date for which is targeted for the Fall of 2003.