Christi A. Walter, Ph.D.Professor & Chair
Florida State University, 1986
Germ cells are the only natural cells capable of establishing a new biological clock. Each offspring is born with a newly minted biological clock regardless of the parents age. Even so, as organisms age, germ cells show reduced genetic stability. We are using transgenic and knockout mouse models, nonhuman primate tissue and human tissue to delineate the mechanisms involved in loss of genetic integrity with age in male germ cells.
Hepatocellular carcinoma occurs at a disproportionately high frequency in Texas. A mouse model that displays spontaneous liver cancer is being used to study the role of DNA repair in the carcinogenic process and potential therapeutic treatments are being investigated.
Mutations in mitochondrial DNA can profoundly effect health and result in disease. We have developed a unique mouse model to study cellular responses to mitochondrial DNA damage and the potential role of mitochondria in aging and diabetes.
Functional spermatogonial stem cells recovered from adult mice.
A) Cross section through a WWv testis showing it is largely devoid of germ cells.
B) WWv testis after transplantation with spermatogonial stem cells isolated from an adult C57BL/6J male mouse. Spermatogenesis is apparent in the three central tubule sections.
C) WWv testis viewed by light microscopy after transplantation. Tubules with spermato - genic colonies appear green.
D) Same WWv testis shown in C, but viewed by fluorescent light. The green fluorescent protein expressing stem cells and derivatives can be seen filling seminiferous tubules winding through the testis.
Dr. Walter lectures in Genes and Development focusing on mitochondrial genetics and DNA repair.
Momand JR, Xu G, Walter CA. The paternal age effect: a multifaceted phenomenon. Biol Reprod. 2013 Apr 25;88(4):108.
Herzig MC, Hildreth K, Huamani J, Perez M, Goins BA, McMahan CA, Reddick RL, Walter CA. Human O6 -methylguanine-DNA methyltransferase containing C145A does not prevent hepatocellular carcinoma in C3HeB/FeJ transgenic mice. Mol Carcinog. 2013 Apr;52(4):275-85.
Xu G, McMahan CA, Hildreth K, Garcia RA, Herbert DC, Walter CA. Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice. Mutat Res. 2012 May 15;744(2):135-9.
Vogel KS, Perez M, Momand JR, Acevedo-Torres K, Hildreth K, Garcia RA, Torres-Ramos CA, Ayala-Torres S, Prihoda TJ, McMahan CA, Walter CA. Age-related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice. Mol Reprod Dev. 2011 Dec;78(12):906-19.
Zhou ZQ, Manguino D, Kewitt K, Intano GW, McMahan CA, Herbert DC, Hanes M, Reddick R, Ikeno Y, Walter CA. Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O6- methylguanine-DNA methyltransferase. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12566-71.
Intano GW, McMahan CA, McCarrey JR, Walter RB, McKenna AE, Matsumoto Y, MacInnes MA, Chen DJ, Walter CA. Base excision repair is limited by different proteins in male germ cell nuclear extracts prepared from young and old mice. Mol Cell Biol. 2002 Apr;22(7):2410-8.
Kim Hildreth, MS