Tor1aflox/flox mice possess loxP sites flanking exons 3-5 of the torsin family 1, member A (torsin A) (Tor1a) gene. TOR1A is an ATPases Associated with diverse Activities (AAA+) protein residing in the lumen of the ER/nuclear envelope (ER/NE) space. An in-frame deletion (ΔE) in TOR1A has been shown to cause the autosomal dominant disorder, DYT1 dystonia, which is characterized by abnormal, involuntary twisting movements and muscle contractions due to selective dysfunction of CNS motor circuits. Mice that are homozygous for this floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-5 deleted in the cre-expressing tissues.
For example, when this floxed line is bred to B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771),cre-mediated recombination in the central and peripheral nervous system results in nestin conditional KO offspring (nestin-Cre;Tor1aflox/- or N-CKO) with abnormal motor behavior, selective areas of neurodegeneration in the central nervous system, and death by P10.
This line can be used in conjunction with mice carrying a ΔE allele (Stock No. 025637) and B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771) to generate the first viable model of primary dystonia with overt twisting movements similar to those seen in the human disease; these animals also exhibit selective areas of neurodegeneration in discrete sensorimotor structures. To generate such nestin selective knock-in mice ("N-SKI"), this line and Stock No. 003771 are first intercrossed to generate animals with one floxed Tor1a allele and the nestin-Cre transgene. These animals are subsequently crossed to this line carrying the ΔE allele (Stock No. 25637) to yield N-SKI Tor1aflox/ΔE Cre+ animals.
