Parp1^{tm1.1(PARP1)Abu}

An attempted knock-in of a mouse gene for its human ortholog instead led to duplication of an upstream gene and insertion of the human gene while leaving the mouse locus unaffected. This occurred when a floxed neomycin cassette was placed within intron 14 of the human PARP1 gene and was subsequently targeted to the mouse locus. During targeting, the upstream and downstream arms were partially digested leaving "sticky" ends that served as template for replication of mouse genomic sequence on the targeting vector. The whole vector then integrated at an adjacent position. Mice carrying this allele were crossed with cre transgenic mice to removed the neomycin cassette. FISH, Q-PCR, and immunoblot analysis determined that the mouse Parp1 locus was unaffected in that it was not duplicated and its expression was normal. One copy of the human PARP1 was inserted and its expression was detectable by immunoblot assays of splenic lysates. The adjacent upstream gene Gm821 was duplicated in this event; duplication of further upstream genomic elements was not investigated. This allele differs from Parp1tm2.1(PARP1)Abu in that no duplication of downstream genes occurred during this targeting event. (J:147608)