My laboratory studies the genetics of testicular germ cell tumor development in mice. Testicular germ cell tumors originate from primordial germ cells and develop within the testis during fetal development. These tumors resemble aspects of testicular cancer in humans.

Testicular germ cell tumors occur spontaneously at an appreciable frequency only in the 129 family of inbred strains of laboratory mice, suggesting strong genetic control. Germ cell tumors in the 129 mouse model were the first tumor models where the tumor cell of origin and the time of transformation were precisely defined. This makes them a very useful model system to study the biology and genetics of testicular tumor development.

Evidence indicates that a large number of genes are responsible for germ cell tumor susceptibility. My laboratory is pursuing several approaches to identify the genes involved in tumor development. We are using chromosome substitution strains (CSS) and congenic strains derived from CSS to map and identify germ cell tumor loci on mouse Chromosome 19. Another approach in the lab is based on analyzing single gene mutations in mice that affect germ cell biology and tumor susceptibility. Using positional cloning approaches, we identified a gene called dead end whose inactivation increases incidence of testicular germ cell tumors. Sequence analysis of dead end encoded protein indicates it is homologous to factors involved in gene editing. Work in my laboratory is geared towards unraveling the function of dead end in primordial germ cells and in testicular cancer. Identification of the genes involved in testicular tumor development and study of their function provides us with fascinating leads both into primordial germ cell biology as well as in tumor development.

Recent publications

• Matin, A. & Nadeau, J.H. (2005) Search for testicular cancer gene hits dead-end. Cell Cycle 4:1000-1002.
  
  
• Youngren K, Coveney D, Peng X, Bhattacharya C, Schmidt LS, Nickerson ML, Lamb B, Deng JM, Behringer RR, Capel B, Rubin E, Nadeau J, Matin A (2005) The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours. Nature 435:360–364.
  
  
• Youngren K., Nadeau JH, Matin A (2003) Testicular cancer susceptibility in the 129.MOLF-Chr 19 mouse strain: additive effects, gene interactions and epigenetic modifications. Hum Mol Genetics 12:389–398.
  
  
• Matin, A., & Nadeau, J.H. (2001) Sensitized polygenic trait analysis. Trends Genet. 17:727–731.
  
  
• Nadeau JH, Singer JB, Matin A, Lander ES (2000) Analyzing complex traits with chromosome substitution strains. Nat Genet 24:221–225.
  
  
• Matin A, Collin GB, Asada Y, Varnum D, Nadeau JH (1999) Susceptibility to testicular germ-cell tumors in a 129.MOLF-Chr 19 chromosome substitution strain. Nat Genet 23:237–240.
  
  
• Matin A, Collin GB, Varnum DS, Nadeau JH (1998) Testicular teratocarcinogenesis in mice–a review. APMIS 106:174–182.
  
  
• Threadgill DW, Yee D, Matin A, Nadeau JH, Magnuson T (1997) Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain. Mamm Genome 8:390–393.
  
  
• Rozmahel R, Wilschanski M, Matin A, Plyte S, Oliver M, Auerbach W, Moore A, Forstner J, Durie P, Nadeau J, Bear C, Tsui LC (1996) Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet 12:280–287.

Last updated 07/18/2007