Strain Name:

B6;129S2-Nr4a1tm1Jmi/J

Stock Number:

006187

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Availability:

Repository- Live

Other products are available, see Purchasing Information for Cryopreserved Embryos

Description

Strain Information

Former Names B6.129S2-Nr4a1tm1Jmi/J    (Changed: 15-OCT-13 )
Type Congenic; Mutant Stock; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   30-MAY-14
Specieslaboratory mouse
GenerationN10+F?+N1pN1 (19-AUG-13)
Generation Definitions
 
Donating Investigator Jeffrey Milbrandt,   Washington University in St. Louis

Description
Mice homozygous for this targeted mutation are viable and fertile, with no gross anatomical or behavioral abnormalities. No transcript is detectable in thymus. Following acute neuroleptic administration with dopamine D2 receptor antagonists (haloperidol and/or raclopride), homozygous mice exhibit reduced catalepsy and disrupted neuropeptide responses in the brain. In homozygotes, adrenal expression of Nr4a2 (also called Nurr1) is increased threefold following LPS challenge. Mutant mice may be useful in studies of antipsychotic drug/neuroleptic therapies, schizophrenia, neurobiology, nuclear receptor family transcription pathways, adrenal gland, and steroidogenesis.

Development
A targeting vector was designed to insert a phosphoglycerate kinase-neomycin resistance cassette (PGK-neo) cassette into the coding region of exon 2 of the Nr4a1 gene (also called Nur77 or NGFI-B). This construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric males were bred with C57BL/6J females to establish heterozygous mice. The donating investigator reports that mutants were bred to C57BL/6 for more than 10 generations and then intercrossed to homozygosity prior to arrival at The Jackson Laboratory (see NSP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome suggested a 129 genetic background, suggesting an incomplete backcross. Four of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Nr4a1
018974   B6N.B6-Tg(Nr4a1-EGFP/cre)820Khog/J
016617   C57BL/6-Tg(Nr4a1-EGFP/cre)820Khog/J
View Strains carrying other alleles of Nr4a1     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Nr4a1tm1Jmi/Nr4a1tm1Jmi

        involves: 129S2/SvPas
  • reproductive system phenotype
  • abnormal uterus physiology
    • change in permeability of uterine vasculature following hormone treatment (E2 + P4) is significantly reduced   (MGI Ref ID J:205553)
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype
    • in homozygous null mice, the adrenal glands and hypothalamic paraventricular nucleus appeared histologically normal relative to wild-type   (MGI Ref ID J:27227)
    • overall, homozygous null mice displayed a normal HPA axis structure, normal basal regulation of hypothalamic and pituitary functions, as well as normal adrenocortical steroidogenesis   (MGI Ref ID J:27227)
  • immune system phenotype
  • *normal* immune system phenotype
    • homozygous null mice exhibited a completely normal thymic and peripheral T cell deletion relative to wild-type   (MGI Ref ID J:77686)
  • cardiovascular system phenotype
  • abnormal vascular permeability
    • change in permeability of uterine vasculature following hormone treatment (E2 + P4) is significantly reduced   (MGI Ref ID J:205553)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Internal/Organ Research
Thymus Defects

Neurobiology Research
Behavioral and Learning Defects
Receptor Defects

Research Tools
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: transcriptional activation
Internal/Organ Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nr4a1tm1Jmi
Allele Name targeted mutation 1, Jeffrey Milbrandt
Allele Type Targeted (Null/Knockout)
Common Name(s) NGFI-B (-); NGFI-B-; Nur77-;
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Nr4a1, nuclear receptor subfamily 4, group A, member 1
Chromosome 15
Gene Common Name(s) GFRP1; Gfrp; HMR; Hbr-1; Hbr1; Hmr; N10; NAK-1; NGFI-B; NGFIB; NP10; NUR77; TIS1; TR3; growth factor response protein; hormone binding receptor 1; hormone receptor;
Molecular Note Exon 2 was disrupted by the insertion of a neomycin resistance gene. Northern blot analysis of total thymic RNA showed an absence of transcript in homozygous mutant mice. [MGI Ref ID J:77686]

Genotyping

Genotyping Information

Genotyping Protocols

Nr4a1tm1Jmi, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lee SL; Wesselschmidt RL; Linette GP; Kanagawa O; Russell JH; Milbrandt J. 1995. Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77). Science 269(5223):532-5. [PubMed: 7624775]  [MGI Ref ID J:77686]

Additional References

Nr4a1tm1Jmi related

Chao LC; Wroblewski K; Zhang Z; Pei L; Vergnes L; Ilkayeva OR; Ding SY; Reue K; Watt MJ; Newgard CB; Pilch PF; Hevener AL; Tontonoz P. 2009. Insulin resistance and altered systemic glucose metabolism in mice lacking Nur77. Diabetes 58(12):2788-96. [PubMed: 19741162]  [MGI Ref ID J:158248]

Crawford PA; Sadovsky Y; Woodson K; Lee SL; Milbrandt J. 1995. Adrenocortical function and regulation of the steroid 21-hydroxylase gene in NGFI-B-deficient mice. Mol Cell Biol 15(8):4331-16. [PubMed: 7623827]  [MGI Ref ID J:27227]

Dai A; Yan G; He Q; Jiang Y; Zhang Q; Fang T; Ding L; Sun J; Sun H; Hu Y. 2012. Orphan nuclear receptor Nur77 regulates androgen receptor gene expression in mouse ovary. PLoS One 7(6):e39950. [PubMed: 22761936]  [MGI Ref ID J:187914]

Ethier I; Beaudry G; St-Hilaire M; Milbrandt J; Rouillard C; Levesque D. 2004. The transcription factor NGFI-B (Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal neuropeptide gene expression. Neuropsychopharmacology 29(2):335-46. [PubMed: 14603264]  [MGI Ref ID J:106200]

Fassett MS; Jiang W; D'Alise AM; Mathis D; Benoist C. 2012. Nuclear receptor Nr4a1 modulates both regulatory T-cell (Treg) differentiation and clonal deletion. Proc Natl Acad Sci U S A 109(10):3891-6. [PubMed: 22345564]  [MGI Ref ID J:182146]

Goddard LM; Murphy TJ; Org T; Enciso JM; Hashimoto-Partyka MK; Warren CM; Domigan CK; McDonald AI; He H; Sanchez LA; Allen NC; Orsenigo F; Chao LC; Dejana E; Tontonoz P; Mikkola HK; Iruela-Arispe ML. 2014. Progesterone receptor in the vascular endothelium triggers physiological uterine permeability preimplantation. Cell 156(3):549-62. [PubMed: 24485460]  [MGI Ref ID J:205553]

Hamers AA; Uleman S; van Tiel CM; Kruijswijk D; van Stalborch AM; Huveneers S; de Vries CJ; van 't Veer C. 2014. Limited role of nuclear receptor Nur77 in Escherichia coli-induced peritonitis. Infect Immun 82(1):253-64. [PubMed: 24166953]  [MGI Ref ID J:206188]

Hamers AA; Vos M; Rassam F; Marinkovic G; Kurakula K; van Gorp PJ; de Winther MP; Gijbels MJ; de Waard V; de Vries CJ. 2012. Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis. Circ Res 110(3):428-38. [PubMed: 22194623]  [MGI Ref ID J:192703]

Hanna RN; Carlin LM; Hubbeling HG; Nackiewicz D; Green AM; Punt JA; Geissmann F; Hedrick CC. 2011. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C(-) monocytes. Nat Immunol 12(8):778-85. [PubMed: 21725321]  [MGI Ref ID J:174432]

Hanna RN; Shaked I; Hubbeling HG; Punt JA; Wu R; Herrley E; Zaugg C; Pei H; Geissmann F; Ley K; Hedrick CC. 2012. NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ Res 110(3):416-27. [PubMed: 22194622]  [MGI Ref ID J:192704]

He QY; Ding LJ; Sun HX; Yu B; Dai AY; Zhang NY; Wang B; Yan GJ; Xu PZ; Hu YL. 2013. FSH modulates the expression of inhibin-alpha and the secretion of inhibins via orphan nuclear receptor NUR77 in ovarian granulosa cells. Mol Reprod Dev 80(9):734-43. [PubMed: 23836374]  [MGI Ref ID J:202247]

Kim SO; Ono K; Tobias PS; Han J. 2003. Orphan nuclear receptor Nur77 is involved in caspase-independent macrophage cell death. J Exp Med 197(11):1441-52. [PubMed: 12782711]  [MGI Ref ID J:121190]

Kiss I; Oskolas H; Toth R; Bouillet P; Toth K; Fulop A; Scholtz B; Ledent C; Fesus L; Szondy Z. 2006. Adenosine A2A receptor-mediated cell death of mouse thymocytes involves adenylate cyclase and Bim and is negatively regulated by Nur77. Eur J Immunol 36(6):1559-71. [PubMed: 16673448]  [MGI Ref ID J:115069]

Lee KW; Cobb LJ; Paharkova-Vatchkova V; Liu B; Milbrandt J; Cohen P. 2007. Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3. Carcinogenesis 28(8):1653-1658. [PubMed: 17434920]  [MGI Ref ID J:124324]

Liu JJ; Zeng HN; Zhang LR; Zhan YY; Chen Y; Wang Y; Wang J; Xiang SH; Liu WJ; Wang WJ; Chen HZ; Shen YM; Su WJ; Huang PQ; Zhang HK; Wu Q. 2010. A unique pharmacophore for activation of the nuclear orphan receptor Nur77 in vivo and in vitro. Cancer Res 70(9):3628-37. [PubMed: 20388790]  [MGI Ref ID J:159367]

Martin LJ; Tremblay JJ. 2010. Nuclear receptors in leydig cell gene expression and function. Biol Reprod 83(1):3-14. [PubMed: 20375256]  [MGI Ref ID J:161974]

Michaud JP; Bellavance MA; Prefontaine P; Rivest S. 2013. Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. Cell Rep 5(3):646-53. [PubMed: 24210819]  [MGI Ref ID J:205530]

Mount MP; Zhang Y; Amini M; Callaghan S; Kulczycki J; Mao Z; Slack RS; Anisman H; Park DS. 2013. Perturbation of transcription factor Nur77 expression mediated by myocyte enhancer factor 2D (MEF2D) regulates dopaminergic neuron loss in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). J Biol Chem 288(20):14362-71. [PubMed: 23536182]  [MGI Ref ID J:198593]

Mullican SE; Zhang S; Konopleva M; Ruvolo V; Andreeff M; Milbrandt J; Conneely OM. 2007. Abrogation of nuclear receptors Nr4a3 andNr4a1 leads to development of acute myeloid leukemia. Nat Med 13(6):730-5. [PubMed: 17515897]  [MGI Ref ID J:121903]

Perez-Sieira S; Martinez G; Porteiro B; Lopez M; Vidal A; Nogueiras R; Dieguez C. 2013. Female Nur77-deficient mice show increased susceptibility to diet-induced obesity. PLoS One 8(1):e53836. [PubMed: 23342015]  [MGI Ref ID J:195699]

Qin L; Zhao D; Xu J; Ren X; Terwilliger EF; Parangi S; Lawler J; Dvorak HF; Zeng H. 2013. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1. Blood 121(11):2154-64. [PubMed: 23315169]  [MGI Ref ID J:195425]

Ramirez-Herrick AM; Mullican SE; Sheehan AM; Conneely OM. 2011. Reduced NR4A gene dosage leads to mixed myelodysplastic/myeloproliferative neoplasms in mice. Blood 117(9):2681-90. [PubMed: 21205929]  [MGI Ref ID J:170358]

St-Hilaire M; Bourhis E; Levesque D; Rouillard C. 2006. Impaired behavioural and molecular adaptations to dopamine denervation and repeated L-DOPA treatment in Nur77-knockout mice. Eur J Neurosci 24(3):795-805. [PubMed: 16930409]  [MGI Ref ID J:112923]

Tessem JS; Moss LG; Chao LC; Arlotto M; Lu D; Jensen MV; Stephens SB; Tontonoz P; Hohmeier HE; Newgard CB. 2014. Nkx6.1 regulates islet beta-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors. Proc Natl Acad Sci U S A 111(14):5242-7. [PubMed: 24706823]  [MGI Ref ID J:208626]

Varga T; Mounier R; Gogolak P; Poliska S; Chazaud B; Nagy L. 2013. Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration. J Immunol 191(11):5695-701. [PubMed: 24133167]  [MGI Ref ID J:207030]

Zhao D; Qin L; Bourbon PM; James L; Dvorak HF; Zeng H. 2011. Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability by targeting endothelial nitric oxide synthase and destabilizing endothelial junctions. Proc Natl Acad Sci U S A 108(29):12066-71. [PubMed: 21730126]  [MGI Ref ID J:174370]

Zheng D; Butler LS; McNamara JO. 1998. Kindling and associated mossy fibre sprouting are not affected in mice deficient of NGFI-A/ NGFI-B genes. Neuroscience 83(1):251-8. [PubMed: 9466414]  [MGI Ref ID J:47060]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are maintained as homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   30-MAY-14
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Nr4a1tm1Jmi  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Nr4a1tm1Jmi x Homozygous for Nr4a1tm1Jmi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Cryopreserved

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Nr4a1tm1Jmi  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Nr4a1tm1Jmi x Homozygous for Nr4a1tm1Jmi  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Cryopreserved

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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