Sex-Specific Quantitative Trait Loci Govern Susceptibility to Theiler's Murine Encephalomyelitis Virus-Induced Demyelination

Sex-Specific Quantitative Trait Loci Govern Susceptibility to Theiler's Murine Encephalomyelitis Virus-Induced Demyelination

Russell J. Butterfield^a, Randall J. Roper^a, Dominic M. Rhein^a, Roger W. Melvold^b, Lia Haynes^c, Runlin Z. Ma^a, R. W. Doerge^d, and Cory Teuscher^e
^a Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois 61802,
^b Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202,
^c Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611,
^d Department of Statistics, Purdue University, West Lafayette, Indiana 47907
^e Department of Medicine, University of Vermont, Burlington, Vermont 05405

Corresponding author: Cory Teuscher, C317 Given Medical Bldg., University of Vermont, Burlington, VT 05405., cteusche{at}zoo.uvm.edu (E-mail)

Communicating editor: Z-B. ZENG

Susceptibility to Theiler's murine encephalomyelitis virus-induceddemyelination (TMEVD), a mouse model for multiple sclerosis(MS), is genetically controlled. Through a mouse-human comparativemapping approach, identification of candidate susceptibilityloci for MS based on the location of TMEVD susceptibility locimay be possible. Composite interval mapping (CIM) identifiedquantitative trait loci (QTL) controlling TMEVD severity inmale and female backcross populations derived from susceptibleDBA/2J and resistant BALBc/ByJ mice. We report QTL on chromosomes1, 5, 15, and 16 affecting male mice. In addition, we identifiedtwo QTL in female mice located on chromosome 1. Our resultssupport the existence of three linked sex-specific QTL on chromosome1 with opposing effects on the severity of the clinical signsof TMEV-induced disease in male and female mice.

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