Dr. Pinkert's research involves gene transfer, expression and regulation using transgenic animal modeling. His work has illustrated the potential of modifying the immune system, enhancing growth performance and the feasibility of biopharmaceutical production (molecular farming). Additionally, a number of enabling technologies and procedures have been developed for the genetic engineering of both nuclear and mitochondrial genomes. Most recently, Dr. Pinkert's laboratory has embarked on pioneering studies revolving around mitochondrial transfer techniques and the development of animals harboring foreign mitochondrial genomes.

In humans, severely debilitating and lethal metabolic and cellular disorders exist due to mutations arising exclusively within the mitochondrial genome.  At present, there are scores of mutations of the mitochondrial genome that are known to be the underlying causes of various degenerative disorders.  These mtDNA mutations, many of which exist in a heteroplasmic state (where both normal and mutant mitochondrial genomes coexist in varying proportions within the same individual), mainly affect tissues with high cellular energy requirements such as brain, optic nerve, cardiac muscle, skeletal muscle, kidney and endocrine organs.  In contrast to nuclear genes, mitochondrial gene replication and function differ markedly in a number of ways – from exclusive matrilineal inheritance of mitochondria and mitochondrial DNA (mtDNA), to the presence of hundreds or thousands of mitochondria (each with one to ten copies of the mitochondrial genome) within a given cell. Various human diseases have been associated with specific mtDNA point mutations, deletions and duplications including diabetes mellitus, myocardiopathy, retinitis pigmentosa, MERRF and MELAS diseases, as well age-associated changes in the functional integrity of mitochondria (as seen in Parkinson's, Alzheimer's and Huntington's diseases).  Therefore, the ability to manipulate the mitochondrial genome and to regulate the expression of mitochondrial genes would provide one possible mode of gene therapy for many of these disease states.  The creation of transmitochondrial mice represents a new model system that will provide a greater understanding of mitochondrial dynamics, leading to therapeutic strategies for human metabolic diseases affected by aberrations in mitochondrial function or mutation.

Pinkert, C.A. and I.A. Trounce. Production of transmitochondrial mice. Methods, 26:348-357, 2002.

Takeda, K., S. Akagi, S. Takahashi, A. Onishi, H. Hanada and C.A. Pinkert. Mitochondrial activity in response to serum starvation in bovine (Bos taurus) cell culture. Cloning & Stem Cells 4:223-230, 2002.

Pinkert, C.A. Transgenic Animal Technology: A Laboratory Handbook. 2nd ed., Academic Press, Inc., San Diego, 2002.

Ingraham, C.A. and C.A. Pinkert. 2003. Developmental fate of mitochondria microinjected into murine zygotes. Mitochondrion 3, 39-46.

McKenzie, M., I.A. Trounce, C.A. Cassar and C.A. Pinkert. 2004. Production of homoplasmic xenomitochondrial mice. Proc. Natl. Acad. Sci. USA 101, 1685-90.

Trounce, I.A., M. McKenzie, C.A. Cassar, C.A. Ingraham, C.A. Lerner, D.A. Dunn, C.OL. Donegan, K. Takeda, W.K. Pogozelski, R.L. Howell and C.A. Pinkert. 2004. Development and initial characterization of xenomitrochondrial mice. J. Bioenerg. Biomembr. 36, 421-427.

Links are to the National Library of Medicine PubMed data base.