title: Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.
abstract: 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.
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Fisher
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Joe
authors.initials: J
authors.lastname: Warren
authors.affiliation: SAGE Labs, A Horizon Discovery Group Company, Saint Louis, MO, United States of America.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Cui
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D008540:Meiosis; D016254:Mutagenesis, Insertional; D009865:Oocytes / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase; C045073:Cre recombinase; D019426:Integrases