Gregory Cox


PhD in Human Genetics from the University of Michigan


My lab takes advantage of the power of mouse genetics and the resources available at The Jackson Laboratory to understand the mechanisms of neuromuscular disease. This information is used to understand the normal function of genes and pathways necessary for motor neuron and skeletal muscle function as well as the processes that go awry in inherited diseases.

Research Interests

The long term goals of my research program are to identify molecular pathways necessary for the normal function and survival of motor neurons and their skeletal muscle targets. Muscular dystrophies and motor neuron diseases collectively have a high impact on health, affecting tens of thousands of people in the United States alone. The diseases are characterized by weakness and progressive wasting of muscles eventually leading to paralysis and death. We have chosen to focus on the resources available at The Jackson Laboratory in the form of spontaneous and induced models of neuromuscular disease as our starting point for gene discovery and functional analysis. This phenotype-driven approach ensures that the mutant genes we identify are critical for the normal development and/or maintenance of motor neurons and skeletal muscles.


Selected Publications

  • Maltecca F, Aghaie A, Schroeder DG, Cassina L, Taylor BA, Phillips SJ, Malaguti M, Previtali S, Guénet JL, Quattrini A, Cox GA, Casari G. 2008. The mitochondrial protease AFG3L2 is essential for axonal development. J. Neurosci. 28: 2827-2836.
  • Lopez MA, Pardo P, Cox GA, Boriek AM. 2008. Early Mechanical Dysfunction of the Respiratory Pump in the Muscular Dystrophy with Myositis (Ttnmdm) Model. Am. J. Physiol. Cell Physiol. Epub doi:10.1152/ajpcell.16.2008 Aug 27, 2008.
  • Ackerman, SL and Cox, GA. 2008. From ER to Eph receptors: new roles for VAP fragments. Cell 133: 949-951.
  • Yang, Y, Mahaffey, CL, Maddatu, TP, Cox, GA, Graber, JH, Frankel, WN. 2007. Deficiency in a brain specific RNA binding protein leads to seizures in a novel mouse model of epilepsy. PLoS Genetics 3: 1275-1283.
  • Seymour RE, Hasham MG, Cox GA, Shultz LD, Hogenesch H, Roopenian DC, Sundberg JP. 2007. Spontaneous mutations in the mouse Sharpin gene result in multiorgan inflammation, immune system dysregulation and dermatitis. Genes Immun. 8: 416-421.
  • Cohen TJ, Waddell DS, Barrientos T, Lu Z, Feng G, Cox GA, Bodine SC, Yao TP. 2007. The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J. Biol. Chem. 282: 33752-33759.
  • Hadano, S, Benn, SC, Kakuta S, Otomo, A, Sudo, K, Kunita, R, Suzuki-Utsunomiya, K, Mizumura, H, Shefner, JM, Cox, GA, Iwakura, Y, Brown, RH Jr, Ikeda, J-E. 2006. Mice Deficient in the Rab5 Guanine Nucleotide Exchange Factor ALS2/alsin Exhibit Age-Dependent Neurological Deficits and Altered Endosome Trafficking. Hum. Mol. Genet. 15: 233-250.
  • Mikaelian, I, Hovick, M, Silva, KA, Burzenski, LM, Shultz, LD, Ackert-Bicknell, CL, Cox, GA, Sundberg, JP. 2006. Expression of terminal differentiation proteins defines stages of mouse mammary gland development. Vet. Pathol. 43: 36-49.
  • Sher, RB, Aoyoma, C, Huebsch, KA, Ji, S, Kerner, K, Yang, Y, Frankel, WN, Hoppel, CL, Wood, PA, Vance, DE, Cox, GA. 2006. A rostrocaudal muscular dystrophy caused by a defect in choline kinase beta, the first enzyme in phosphatidylcholine biosynthesis. J. Biol. Chem. 281: 4938-4948.
  • Runkel, F, Büssow, H, Seburn KL, Cox, GA, McVeigh Ward, D, Kaplan, J, Franz, T. 2006. Grey, a novel mutation in the murine Lyst gene causes the beige phenotype by skipping of exon 25. Mamm. Genome 17: 203-210.
  • Seburn, KL, Nangle, LA, Cox, GA, Schimmel, P, Burgess, RW. 2006. A mouse model of Charcot Marie Tooth 2D indicates sensory and motor neuropathy and a novel pathogenic function for the mutant protein. Neuron 51: 715-726.
  • Wooley, CM, Sher, RB, Frankel, WN, Cox, GA, and Seaburn, KL. 2005. SOD1 mice have subtle gait defects prior to the appearance of overt symptoms. Muscle and Nerve 32: 43-50.
  • Lee Y, Kameya S, Cox GA, Hsu J, Hicks W, Maddatu TP, Smith RS, Naggert JK, Peachey NS, and Nishina PM. 2005. Ocular abnormalities in Largemyd and Largevls mice, spontaneous models for muscle, eye, brain diseases. Mol. Cell Neurosci. 30: 160-172.
  • Huebsch KA, Kudryashova E, Wooley CM, Sher RB, Seburn KL, Spencer MJ, Cox GA. 2005. mdm Muscular Dystrophy: Interactions with Calpain 3 and a Novel Functional Role for Titin’s N2A Domain. Hum. Mol. Genet. 14: 2801-2811.
  • Maddatu, TP, Garvey, SM, Schroeder, DG, Zhang, W, Kim, S-Y, Nicholson, AI, Davis, CJ, Cox, GA. 2005. Dilated cardiomyopathy (DCM) in the nmd mouse: Transgenic rescue and QTLs that improve cardiac function and survival. Hum. Mol. Genet. 14: 3179-3189.
  • Tarchini B, Hanh T, Huynh N, Cox GA and Duboule D. 2005. HoxD cluster scanning deletions identify multiple defects leading to paralysis in the mouse mutant Ironside. Genes Dev. 19: 2862-2876.
  • Maddatu TP, Garvey SM, Shroeder DG, Hampton TG, Cox GA. 2004. Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy. Hum. Mol. Genet. 13: 1105-1115.
  • Sundberg JP, Silva KA, Li R, Cox GA, King LE. 2004. Adult onset alopecia areata is a complex polygenic trait in the C3H/HeJ mouse model. J. Invest. Dermatol. 123: 294-297.
  • Ho M, Post CM, Donahue LR, Lidov HGW, Bronson RT, Goolsby H, Watkins SC, Cox GA, Brown RH Jr. 2004. Disruption of muscle membrane and phenotype divergence in two mouse models of dysferlin-deficiency. Hum. Mol. Genet. 13: 1999-2010.
  • Sundberg JP, Boggess D, Silva KA, McElwee KJ, King LE, Li R, Churchill G, Cox GA. 2003. Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice. J. Invest. Dermatol. 120: 771-775.
  • Serreze DV, Pierce MA, Post CM, Chapman HD, Savage H, Bronson RT, Rothman PB, Cox GA. 2003. Paralytic autoimmune myositis develops in addition to type 1 diabetes in NOD mice made Th1 cytokine deficient by expression of an IFNγ receptor β chain transgene. J. Immunology 170: 2742-2749.
  • Garvey SM, Rajan, C, Lerner AP, Frankel WN, Cox GA. 2002. The Muscular Dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin. Genomics 79: 146-149.
  • Cox GA, Mahaffey CL, Nystuen A, Letts VA, Frankel WN. 2000. The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development. Nature Genetics 26: 198-202.
  • Sundberg JP, Boggess D, Shultz LD, Fijneman RJ, Demant P, HogenEsch H, Cox GA. 2000. The chronic proliferative dermatitis mouse mutation (cpdm): mapping of the mutant gene locus. J. Exp. Anim. Sci. 41: 101-108.
  • Lumeng CN, Phelps SF, Rafael JA, Cox GA, Hutchinson TL, Begy CR, Adkins E, Wiltshire R, Chamberlain JS. 1999. Characterization of dystrophin and utrophin diversity in the mouse. Hum. Mol. Genet. 8:593-599.
  • Cox GA, Mahaffey CL, Frankel WN. 1998. Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. Neuron 21: 1327-1337
  • Cox GA, Lutz CM, Yang C-L, Biemesderfer D, Bronson RT, Fu A, Aronson PS, Noebels JL, Frankel WN. 1997. Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice. Cell 91: 139-148.
  • Chamberlain JS, Corrado K, Rafael JA, Cox GA, Hauser M, Lumeng C. 1997. Interactions between dystrophin and the sarcolemma membrane. In: Cytoskeletal Regulation of Membrane Function (ed. Froehner SC and Bennett V, The Rockefeller University Press, New York): 19-29.
  • Rafael JA, Cox GA, Corrado K, Jung D, Campbell KP, Chamberlain JS. 1996. Forced expression of dystrophin deletion constructs reveals structure-function correlations. J. Cell Biol. 134: 93-102.
  • Denetclaw WF, Jr., Hopf FW, Cox GA, Chamberlain JS, Steinhardt RA. 1994. Myotubes from transgenic mdx mice expressing full-length dystrophin show normal calcium regulation. Mol. Biol. Cell 5: 1159-1167.
  • Cox GA, Sunada Y, Campbell KP,. Chamberlain JS. 1994. Dp71 can restore the dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy. Nature Genetics 8: 333–339.
  • Cox GA, Phelps SF, Chapman VM, Chamberlain JS. 1993. New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nature Genetics 4: 87–93.
  • Cox GA, Cole NM, Matsumura K, Phelps SF, Hauschka SD, Campbell KP, Faulkner JA, Chamberlain JS. 1993. Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. Nature 364: 725–729.
  • Chamberlain JS, Phelps SF, Cox GA, Maichele AJ, Greenwood AD. 1993. PCR analysis of muscular dystrophoy in mdx mice. In: Molecular and Cell Biology of Muscular Dystrophy, Partridge T (ed), Chapman & Hall. 167-189.
  • Chamberlain JS, Farwell NJ, Ranier JE, Cox GA, Caskey CT. 1991. PCR analysis of dystrophin gene mutation and expression. J. Cell Biochem. 46: 255–259.

Dissertation Students

Paige Martin

Ambreen Sayed