Primary Department Affiliation: Biochemistry and Molecular Genetics
LAB RESEARCH FOCUS: Mouse Models of Human Genetic Disorders
The combination of gene targeting and embryonic stem (ES) cell technologies allows the introduction of precise alterations into the mouse germline. Gene targeting involves the alteration of a gene in cultured cells by homologous recombination between the endogenous gene and a modified clone of the gene. The modified cells are then introduced into a murine embryo and contribute to the tissues of the developing mouse. The modification may be transmitted to progeny to create a strain of mice harboring a desired genetic alteration.
My work has focused on improving methods of gene targeting. Prior to coming to UAB, I developed a method of repeatedly targeting genes in ES cells. The method allowed me to replace the -globins expressed in adult mouse with the human -globin allele responsible for sickle cell anemia.
My laboratory will use ES cell technology to study human disorders associated with the expansion of nucleotide repeats. Huntington's disease (HD), an example of one of these diseases, is an autosomal dominant disorder causing irreversible neural degeneration. Recently, the gene responsible for HD was cloned. Affected individuals differ from normal by having a greater number of CAG repeats near the beginning of this gene. Onset of the disease usually occurs after reproductive age (30-60 yrs.) and the age of onset may be inversely related to the number of repeats. The biochemical function of the disease gene, the pathology of the disease at the molecular level, and the mechanism by which the repeats expand is not yet known. We will use culture systems and mouse models to investigate the mechanism of repeat expansion as well as the pathological consequences of these expansions. These experiments may reveal important information regarding the increasing number of diseases associated with repeat expansion, including: fragile X- syndrome, myotonic dystrophy, and spinobulbar muscular atrophy.
Peter J. Detloff (b. 1963) received his B.S. degree in Biochemistry from the University of Illinois at Champaign Urbana in 1985 and his Ph.D. degree from the University of Chicago in 1991. He was a postdoctoral fellow with Professor Oliver Smithies in the Department of Pathology in the School of Medicine at the University of North Carolina at Chapel Hill. In 1993 he joined UAB as an Assistant Professor in the Department of Biochemistry and Molecular Genetics.