Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus
Jonas Lindeberg
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Jonas Lindeberg and Dmitry Usoskin contributed equally to the work.
Search for more papers by this authorDmitry Usoskin
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Jonas Lindeberg and Dmitry Usoskin contributed equally to the work.
Search for more papers by this authorHenrik Bengtsson
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorAnna Gustafsson
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorAnnika Kylberg
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorStine Söderström
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Ted Ebendal
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Box 587, SE-751 23 Uppsala, SwedenSearch for more papers by this authorJonas Lindeberg
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Jonas Lindeberg and Dmitry Usoskin contributed equally to the work.
Search for more papers by this authorDmitry Usoskin
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Jonas Lindeberg and Dmitry Usoskin contributed equally to the work.
Search for more papers by this authorHenrik Bengtsson
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorAnna Gustafsson
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorAnnika Kylberg
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorStine Söderström
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Ted Ebendal
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Uppsala, Sweden
Department of Neuroscience, Developmental Neuroscience Unit, Uppsala University, Biomedical Center, Box 587, SE-751 23 Uppsala, SwedenSearch for more papers by this authorAbstract
Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3′-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development. genesis 40:67–73, 2004. © 2004 Wiley-Liss, Inc.
LITERATURE CITED
- Althini S, Bengtsson H, Usoskin D, Söderström S, Kylberg A, Lindqvist E, Chuva de Sousa Lopes S, Olson L, Lindeberg J, Ebendal T. 2003. Normal nigrostriatal innervation but dopamine dysfunction in mice carrying hypomorphic tyrosine hydroxylase alleles. J Neurosci Res 72: 444–453.
- Baetge G, Gershon MD. 1989. Transient catecholaminergic cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons. Dev Biol 132: 189–211.
- Banerjee SA, Hoppe P, Brilliant M, Chikaraishi DM. 1992. 5′ flanking sequences of the rat tyrosine hydroxylase gene target accurate tissue-specific, developmental, and transsynaptic expression in transgenic mice. J Neurosci 12: 4460–4467.
- Bengtsson H, Soderstrom S, Ebendal T. 1995. Expression of activin receptors type I and II only partially overlaps in the nervous system. Neuroreport 7: 113–116.
- Czyzyk-Krzeska MF, Beresh JE. 1996. Characterization of the hypoxia-inducible protein binding site within the pyrimidine-rich tract in the 3′-untranslated region of the tyrosine hydroxylase mRNA. J Biol Chem 271: 3293–3299.
- Dymecki SM. 1996. Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci U S A 93: 6191–6196.
- Foster GA, Schultzberg M, Dahl D, Goldstein M, Verhofstad AAJ. 1985. Ephemeral existence of a single catecholamine synthetic enzyme in the olfactory placode and the spinal chord of the embryonic rat. Int J Dev Neurosci 3: 597–608.
- Fujii T, Sakai M, Nagatsu I. 1994. Immunohistochemical demonstration of expression of tyrosine hydroxylase in cerebellar Purkinje cells of the human and mouse. Neurosci Lett 165: 161–163.
- Gelman DM, Noain D, Avale ME, Otero V, Low MJ, Rubinstein M. 2003. Transgenic mice engineered to target Cre/loxP-mediated DNA recombination into catecholaminergic neurons. genesis 36: 196–202.
- Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JL, Jones KR. 2002. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci 22: 6309–6314.
- Huang S, Tang B, Usoskin D, Lechleider RJ, Jamin SP, Li C, Anzano MA, Ebendal T, Deng C, Roberts AB. 2002. Conditional knockout of the Smad1 gene. genesis 32: 76–79.
- Iwata N, Kobayashi K, Sasaoka T, Hidaka H, Nagatsu T. 1992. Structure of the mouse tyrosine hydroxylase gene. Biochem Biophys Res Commun 182: 348–354.
- Jaeger CB, Joh TH. 1983. Transient expression of tyrosine hydroxylase in some neurons of the developing inferior colliculus of the rat. Brain Res 313: 128–132.
- Jonakait GM, Markey KA, Goldstein M, Black IB. 1984. Transient expression of selected catecholaminergic traits in cranial sensory and dorsal root ganglia of the embryonic rat. Dev Biol 101: 51–60.
- Komori K, Sakai M, Karasawa N, Yamada K, Nagatsu I. 1991. Evidence for transient expression of tyrosine hydroxylase immunoreactivity in the mouse striatum and the effects of colchicine. Acta Histochem Cytochem 24: 223–231.
- Laird PW, Zijderveld A, Linders K, Rudnicki MA, Jaenisch R, Berns A. 1991. Simplified mammalian DNA isolation procedure. Nucleic Acids Res 19: 4293.
- Lee KJ, Dietrich P, Jessell TM. 2000. Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403: 734–740.
- Lindeberg J, Ebendal T. 1999. Use of an internal ribosome entry site for bicistronic expression of Cre recombinase or rtTA transactivator. Nucleic Acids Res 27: 1552–1554.
- Min N, Joh TH, Kim KS, Peng C, Son JH. 1994. 5′ upstream DNA sequence of the rat tyrosine hydroxylase gene directs high-level and tissue-specific expression to catecholaminergic neurons in the central nervous system of transgenic mice. Brain Res Mol Brain Res 27: 281–289.
- Mountford PS, Smith AG. 1995. Internal ribosome entry sites and dicistronic RNAs in mammalian transgenesis. Trends Genet 11: 179–184.
-
Nagy A.
2000.
Cre recombinase: the universal reagent for genome tailoring.
genesis
26:
99–109.
10.1002/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- Sasaoka T, Kobayashi K, Nagatsu I, Takahashi R, Kimura M, Yokoyama M, Nomura T, Katsuki M, Nagatsu T. 1992. Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice. Brain Res Mol Brain Res 16: 274–286.
- Satoh J, Suzuki K. 1990. Tyrosine hydroxylase-immunoreactive neurons in the mouse cerebral cortex during the postnatal period. Dev Brain Res 53: 1–5.
- Schimmel JJ, Crews L, Roffler TS, Chikaraishi DM. 1999. 4.5 kb of the rat tyrosine hydroxylase 5′ flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors. Brain Res Mol Brain Res 74: 1–14.
- Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70–71.
- Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, Harvey RP. 2002. Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3′UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol 46: 431–439.
- Teitelman G, Gershon MD, Rothman TP, Joh TH, Reis DJ. 1981a. Proliferation and distribution of cells that transiently express a catecholaminergic phenotype during development in mice and rats. Dev Biol 86: 348–355.
- Teitelman G, Joh TH, Reis DJ. 1981b. Transformation of catecholaminergic precursors into glucagon (A) cells in mouse embryonic pancreas. Proc Natl Acad Sci U S A 78: 5225–5229.
- Versaux BC, Verney C, Zecevic N, Nguyen LJ. 1992. Early appearance of tyrosine hydroxylase immunoreactivity in the retina of human embryos. Brain Res Dev Brain Res 69: 283–287.
- Wulle I, Schnitzer J. 1989. Distribution and morphology of tyrosine hydroxylase-immunoreactive neurons in the developing mouse retina. Brain Res Dev Brain Res 48: 59–72.
- Zecevic N, Verney C. 1995. Development of the catecholamine neurons in human embryos and fetuses, with special emphasis on the innervation of the cerebral cortex. J Comp Neurol 351: 509–535.
- Zinyk DL, Mercer EH, Harris E, Anderson DJ, Joyner AL. 1998. Fate mapping of the mouse midbrain-hindbrain constriction using a site-specific recombination system. Curr Biol 8: 665–668.
