Tg(HTT*97Q)IXwy

The 240 kb human bacterial artificial chromosome BAC(RP11-866L6), containing the entire 170 kb human Huntingtin (htt) genomic locus and approximately 20 kbp of 5' and 50 kbp of 3' flanking sequences, was modified by replacing the human htt exon 1 with a loxP-flanked human mutant htt exon 1 sequence (containing 97 mixed CAA-CAG repeats encoding a continuous polyglutamine (polyQ) stretch). DNA from a modified BAC clone was used as the source for the BACHD transgene and microinjected into FVB fertilized eggs. Mice from founder line BACHD-I were found to express relatively high levels of full-length human mutant Huntingtin (fl-mhtt) in the brain by qRT-PCR and the mice harbor tandem integrands of approximately 5 copies of the transgene. Another line, named BACHD-L, was analyzed, showing that the phenotypic aspects of line I were replicated in this strain. (J:137345)