Dopamine neuron agenesis in Nurr1-deficient mice

Science

Volumn 276, Issue 5310, 1997, Pages 248-250

  Zetterström, Rolf H ^a   Solomin, Ludmila ^b   Jansson, Lottie ^b   Hoffer, Barry J ^c   Olson, Lars ^a   Perlmann, Thomas ^b  

^a KAROLINSKA INSTITUTE   (Sweden)

^b LUDWIG INSTITUTE FOR CANCER RESEARCH   (Sweden)

^c NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOPAMINE; DOPAMINE RECEPTOR;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; DOPAMINE BRAIN LEVEL; DOPAMINERGIC NERVE CELL; MESENCEPHALON; MOUSE; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

3,4-DIHYDROXYPHENYLACETIC ACID; ANIMALS; CELL DIFFERENTIATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CORPUS STRIATUM; DNA-BINDING PROTEINS; DOPAMINE; GENE TARGETING; HETEROZYGOTE; LIGANDS; MESENCEPHALON; MICE; NERVE TISSUE PROTEINS; NEURONS; RNA, MESSENGER; TRANSCRIPTION FACTORS;

ANIMALIA;

EID: 0031002024     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.276.5310.248     Document Type: Article

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33. Gene targeting experiments were made essentially as described [A. L. Joyner, Ed., Gene Targeting: A Practical Approach (Oxford Univ. Press, Oxford, 1993)]. Genomic Nurr1 sequences were doned from a mouse 129 genomic library, and sequences (Fig. 1A) were inserted into a targeting vector (pMC1NeoPolyA, Stratagene, La Jolla, CA) that contained a neomycin phosphotransferase gene driven by a herpes simplex virus thymidine kinase gene promoter. Plasmid sequences were excised and the targeting construct was transfected into E14 embryonic stem (ES) cells. G418-resistant clones in which Nurr1 had been targeted were identified by Southern (DNA) blotting, using a 1-kb Nurr1 probe located 5′ of Nurr1 sequences in the targeting construct, ensuring that the authentic Nurr1 locus was detected. ES cells from three independent clones were injected into C57Bl6 recipient blastocysts to obtain germline transmission. The reported phenotype was confirmed with two independent ES cell lines. Resulting animals and embryos were genotyped by means of polymerase chain reactions specific for the wild-type (5′-GTCGGTTTCAGAAGTGC-3′ and 5′-GTAACGACCTCTCCGG-3′) and targeted allele (5′-CCAATGTCGAGCAAACC-3′ and 5′-CGATCCCCTCAGAAGAA-3′), respectively.
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35. We thank B. Vennström for advice and the generous gift of an ES cell line-derived genomic DNA library and R. Undahl and D. Dahl for generous gifts of ADH2-and neurofilament antisera, respectively. For excellent technical assistance, we acknowledge A. Foo, E. Nilsson, E. Lindqvist, K. Lundströmer, and K. Nordström. We thank U. Lendahl for advice and R. Pettersson for valuable comments on the manuscript. Supported by the Swedish Medical Research Council and the U.S. Public Health Service.