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研究领域

Molecular basis of mammalian spermatogenesis – Gametogenesis involves production of male and female germ cells required for maintenance of a species. In addition to its inherent interest, study of gametogenesis is also useful to investigate a wide range of important cell biology processes found in most organs including cell-cell communication, stem cell biology, meiosis, cellular differentiation and cellular adhesion. Gametogenesis is also important from an applied research perspective as approximately 15% of couples are infertile. New information about the gene products required for gametogenesis could be applied to diagnosis and treatment of infertility. In addition, such information may provide opportunities for development of new drugs that could be used for non-hormonal female and male contraceptives. There are four current areas of research in the lab. The first involves the function of a novel family of proteins (FNDC3) in mammalian development and reproduction. The second project concerns investigating of the function of post-translational modification of tubulin in spermatogenesis. The third area, is a long-term collaboration with the Wallace lab to investigate the function of mitochondrial-localized proteins in mammalian development and reproduction. Each of these projects uses the mouse as a model system. Lastly, a new project concerns development of methods to produce oocytes form human ES cells.

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Strong MK, Southwell AL, Yonan JM, Hayden MR, MacGregor GR, Thompson LM, Steward O. (2013) Age-dependent resistance to excitotoxicity in Htt CAG140 mice and the effect of strain background. Journal of Huntington’s Disease 2, 221-241. Lin CS, Sharpley MS, Fan WW, Waymire KG, Sadun AA, Carelli V, Ross-Cisneros FN, Baciu P, McManus MJ, Pan BX, Gil DW, MacGregor GR, Wallace DC (2012) Mouse mtDNA mutant model of Leber hereditary optic neuropathy. Proc. Natl. Acad. Sci. (USA)109, 20065 – 20070. Sharpley MS, Marciniak C, Eckel-Mahan K, McManus M, Waymire KG, Crimi M, Lin CS, Masubuchi S, Friend N, Koike M, Chalkia M, MacGregor GR, Sassone-Corsi P and Wallace DC (2012) Maternal inheritance of two different mouse mtDNAs is genetically stable and results in altered behavior and cognition. Cell 151, 333-343. Fielder TJ, Yi CS, Masumi J, Waymire KG, Chen H-W, Wang S, Shi, K-X, Wallace, DC, MacGregor G.R. (2012) Comparison of male chimeric mice generated from microinjection of JM8.N4 embryonic stem cells into C57BL/6J and C57BL/6NTac blastocysts. Transgenic Research 18, DOI 10.1007/s11248-012-9605-3 Navarro SJ, Trinh T, Lucas CA, Ross AJ, Waymire KG, MacGregor GR (2012) The C57BL/6J mouse stain background modifies the effect of a mutation in Bcl2l2. G3 : Genes, Genomes, Genetics 2, 99-102. Nicholson A., Reifsnyder P., Malcolm R., Lucas C., MacGregor G.R., Zhang W. and Leiter E. (2010) Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide nucleotide transhydrogenase (Nnt) gene. Obesity Published online January 7, 2010 (doi: 10.1038/oby.2009.477) Ikegami K., Horigome, D., Mukai, M., Livnat, I., MacGregor, G.R., and Setou, M. (2008) TTLL10 is a protein polylgycylase that can modify nucleosome assembly protein 1 FEBS Lett. 582, 1129-1134. Fan, W.-W., Waymire, K.G., Narula, N., Li, P., Rocher, C., Coskun, P.E., Vannan, M.A., Narula, J., MacGregor, GR, Wallace, D.C. (2008) A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations.Science 319, 958 – 962. Ikegami K, , Heier RL, Taruishi M, Takagi H, Mukai M, Shimma S, Taira S, Hatanaka K, Morone N, Yao I, Campbell PK, Yuasa S, Janke C, MacGregor GR*, and Setou M* (2007) Loss of Alpha Tubulin Polyglutamylation in ROSA22 Mice is Associated with Abnormal Targeting of KIF1A and Modulated Synaptic Function (*co-corresponding authors) Proc. Natl. Acad. Sci. (USA) 104, p3213 – 3218. Obholz KL, Akopyan AA, Waymire KG, MacGregor GR (2006) FNDC3A is required for adhesion between spermatids and Sertoli cell in mice. Developmental Biology 298, 498-513.

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