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J. Biol. Chem., Vol. 279, Issue 10, 9389-9391, March 5, 2004

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CAG Repeat Lengths in X- and Y-bearing Sperm Indicate That Gender Bias during Transmission of Huntington's Disease Gene Is Determined in the Embryo^*

Irina V. Kovtun, Glenn Welch, H. David Guthrie, Kari L. Hafner¶, and Cynthia T. McMurray||**

From the Departments of Molecular Pharmacology and Experimental Therapeutics, ^||Biochemistry and Molecular Biology, and ^**Molecular Neuroscience Program, ^¶Molecular Cytogenetics, Mayo Clinic and Foundation, Rochester, Minnesota 55905 and Germplasm and Gamete Physiology Laboratory, United States Department of Agriculture, Beltsville, Maryland 20705

The size of the CAG tract at the Huntington's disease (HD) locus upon transmission depends on the gender of the parent. However, the basis for the parent-of-origin effect is unknown. To test whether expansion and contraction in HD are "imprinted" in the germ cells, we isolated the X- and Y-bearing sperm of HD transgenic mice. Here we show that CAG repeat distributions in the X- and Y-bearing spermatozoa of founding fathers do not differ. These data show that gender-dependent changes in CAG repeat length arise in the embryo.

Received for publication, December 1, 2003

^* This work was supported by the Mayo Foundation, the Hereditary Disease Foundation, and National Institutes of Health Grant NS4073802S1 (to C. T. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, MN 55905. Tel.: 507-284-1597; Fax: 507-284-9111; E-mail: mcmurray.cynthia{at}mayo.edu.

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