mouse strain Ptf1a{tm1(tTAoff)Macd} mouse strain A mouse strain in which part or all of the targeted gene, pancreas specific transcription factor, 1a (NCBI Gene ID: 19213) is replaced to create Ptf1a{tTA} using the Loxed Cassette Acceptor allele Ptf1a{tm1(LCA)}). Mice heterozygous for the tTA replacement of the Ptf1a gene are viable, fertile, of normal size, and do not display any behavioral abnormalities. The replacement places the expression of tTAoff (Gossen & Bujard, PNAS 89:5547, 1992) under the control of the regulatory sequences of the endogenous Ptf1a gene. This mouse was initially designed to be mated to a mouse (see BCBC #M461) bearing a bicistronic Ptf1a-lacZ transgene driven by the tetracycline-regulatory element (TRE: 7 copies of tetO with the CMV minimal promoter). For offspring homozygous for the tTA allele of Ptf1a and hemi- or homozygous for the transgene, the production of PTF1a is due solely to tTA-activation of the transgene, which is repressed by administration of tetracycline/doxycycline. This strategy allows embryonic developmental arrest at desired stages or cessation of gene function in adult mice for the pancreas (similar to that for Pdx1 described in Holland et al., PNAS 99:12236, 2002) and also for the cerebellum, retina, dorsal spinal cord and possibly hypothalamus. This transgenic mouse may be useful in studies of pancreatic endocrine/exocrine development and function, diabetes, and certain defects of the CNS. This tissue-specific expresser of tTA can also be bred with strains bearing other TRE-transgenes for organ-specific conditional expression analyses. Nearly all of the Ptf1a transcription unit has been replaced by a tTAoff coding sequence with accessory translational and RNA-processing signals, as follows, from 5' to 3': the Ptf1a gene transcriptional start and 49-bp of its 5'UTR; the Xenopus laevis beta-globin 5'UTR with Kozak initiator codon; the tTA coding sequence; and a 990-bp rabbit beta-globin gene fragment encoding the last 14-bp of its second exon, the 573-bp second intron, and the 364-bp last exon including a 98-bp 3'UTR with the polyA addition signal and addition site, and 39-bp of 3' beta-globin gene flanking sequence. The Ptf1a locus was modified by recombination-mediated cassette exchange using the cassette exchange allele in Ptf1a-LCA ES cells (Burlison et al., submitted). Person: Mark A. Magnuson, Jill Lindner, Jean-Philippe Cartailler Ptf1a{tm1(tTAoff)Macd} Vanderbilt University Medical Center