PMID- 26886559 OWN - NLM STAT- MEDLINE DCOM- 20160802 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 2 DP - 2016 TI - Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons. PG - e0149379 LID - 10.1371/journal.pone.0149379 [doi] LID - e0149379 AB - The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease. FAU - Liu, Zhenyi AU - Liu Z AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. FAU - Brown, Andrew AU - Brown A AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. FAU - Fisher, Dan AU - Fisher D AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. FAU - Wu, Yumei AU - Wu Y AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. FAU - Warren, Joe AU - Warren J AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. FAU - Cui, Xiaoxia AU - Cui X AD - SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America. LA - eng PT - Journal Article DEP - 20160217 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM EIN - PLoS One. 2019 Jun 20;14(6):e0218976. PMID: 31220192 MH - Alleles MH - Animals MH - Brain/*metabolism MH - Dopamine Plasma Membrane Transport Proteins/*metabolism MH - Dopaminergic Neurons/*metabolism MH - Embryo, Mammalian/metabolism MH - Germ Cells/metabolism MH - Humans MH - Integrases/*metabolism MH - Meiosis MH - Mutagenesis, Insertional MH - Oocytes/metabolism MH - *Organ Specificity MH - Rats MH - Substantia Nigra/metabolism MH - Tyrosine 3-Monooxygenase/genetics/*metabolism MH - Ventral Tegmental Area/metabolism PMC - PMC4757100 COIS- Competing Interests: All authors are full time employees of Horizon Discovery Group Company, which creates and markets genetically engineered rodent and rabbit models, including these Cre rats. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. EDAT- 2016/02/18 06:00 MHDA- 2016/08/03 06:00 PMCR- 2016/02/17 CRDT- 2016/02/18 06:00 PHST- 2015/05/07 00:00 [received] PHST- 2016/02/01 00:00 [accepted] PHST- 2016/02/18 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/08/03 06:00 [medline] PHST- 2016/02/17 00:00 [pmc-release] AID - PONE-D-15-16891 [pii] AID - 10.1371/journal.pone.0149379 [doi] PST - epublish SO - PLoS One. 2016 Feb 17;11(2):e0149379. doi: 10.1371/journal.pone.0149379. eCollection 2016.