Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation F?+F2pN1 Generation Definitions   Donating Investigator Alcino J. Silva,   University of California, Los Angeles

Description
Homozygous "floxed B-raf" (B-raf^f/f) mice are viable and fertile with normal B-raf protein expression. When bred to mice expressing Cre recombinase under the control of a promoter of interest, exon 12 of the targeted gene is deleted in the tissue of interest. These mutant mice may be useful in neurological studies such as Ras/Raf and MEK/ERK signaling, synaptic (neural) plasticity, learning and memory.

For example, when crossed to a strain expressing Cre recombinase in nervous tissue (see Stock No. 003771), this mutant mouse strain may be useful in studies of neuron development.

For example, when crossed to a strain expressing interferon inducible Cre recombinase (see Stock No. 003755), this mutant mouse strain may be useful in studies of extraembryonic mammmalian development.

Development
A targeting vector was designed to place loxP sites on both sides of exon 12 (the first exon that encodes the B-raf kinase domain) of the targeted gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were used to generate chimeric males. These mice were maintained by backcrossing on a 129T2/SvEmsJ (Stock No. 002065) inbred genetic background for at least 9 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	002065 129T2/SvEmsJ
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Braf

017837	B6.129P2(Cg)-Braftm1Mmcm/J
013590	B6.Cg-Braftm1Mmcm Ptentm1Hwu Tg(Tyr-cre/ERT2)13Bos/BosJ

View Strains carrying other alleles of Braf     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Cardiofaciocutaneous Syndrome   (BRAF) Leopard Syndrome 3   (BRAF) Lung Cancer   (BRAF) Noonan Syndrome 7; NS7   (BRAF)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Braf^tm1Sva/Braf^tm1.1Sva Tg(Nes-cre)1Kln/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL   (conditional)

• mortality/aging
• partial lethality at weaning
  • mice tend to die in third week postnatal, although some survive to P35   (MGI Ref ID J:121660)
• growth/size phenotype
• decreased body weight
  • at P32, body weight is ~25% of littermates   (MGI Ref ID J:121660)
• postnatal growth retardation
  • from P12-14 onwards, mice show severe growth retardation   (MGI Ref ID J:121660)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • mice show normal nociceptive response in hotplate assay   (MGI Ref ID J:121660)
• • hyperactivity
    • mice appear hyperactive   (MGI Ref ID J:121660)
• nervous system phenotype
• *normal* nervous system phenotype
  • dorsal root ganglion neurons survive in mutants   (MGI Ref ID J:121660)
• • abnormal adenohypophysis morphology
    • perivascular hypothalamic axonal innervation is reduced   (MGI Ref ID J:121660)
  • • small adenohypophysis
      • anterior lobe of pituitary gland is markedly reduced in size compared to controls   (MGI Ref ID J:121660)
  • thin cerebral cortex
    • disproportionate thinning of cortex is observed   (MGI Ref ID J:121660)
• endocrine/exocrine gland phenotype
• abnormal adenohypophysis morphology
  • perivascular hypothalamic axonal innervation is reduced   (MGI Ref ID J:121660)
• • small adenohypophysis
    • anterior lobe of pituitary gland is markedly reduced in size compared to controls   (MGI Ref ID J:121660)
• homeostasis/metabolism phenotype
• abnormal body temperature homeostasis
  • when separated from other mice, body temperature drops rapidly   (MGI Ref ID J:121660)
• abnormal growth hormone level
  • level is elevated in pituitary relative to controls   (MGI Ref ID J:121660)
  • level of growth hormone is elevated in individual pituitary endocrine cells   (MGI Ref ID J:121660)
• hypoglycemia
  • mice display significantly reduced bolood glucose levels   (MGI Ref ID J:121660)

Braf^tm1Sva/Braf^tm1.1Sva Meox2^tm1(cre)Sor/Meox2⁺

        involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ   (conditional)

• mortality/aging
• complete lethality at weaning
  • although born alive death occurs around 21 days of age from aggressive neurodegenerative disease   (MGI Ref ID J:105998)
• growth/size phenotype
• postnatal growth retardation
  • after being born alive, pups show progressive growth retardation   (MGI Ref ID J:105998)

View Research Applications

Research Applications

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

Cell Biology Research
Signal Transduction

Neurobiology Research
Behavioral and Learning Defects
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cell Biology Research
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Braftm1Sva
Allele Name		targeted mutation 1, Alcino J Silva
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		B-raff;
Mutation Made By		Rachel Chen,   University of California, Los Angeles
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Braf, Braf transforming gene
Chromosome		6
Gene Common Name(s)		9930012E13Rik; AA120551; AA387315; AA473386; B-RAF1; BRAF1; Braf transforming gene 2; Braf-2; Braf2; C87398; D6Ertd631e; DNA segment, Chr 6, ERATO Doi 631, expressed; NS7; RAFB1; RIKEN cDNA 9930012E13 gene; expressed sequence AA120551; expressed sequence AA387315; expressed sequence AA473386; expressed sequence C87398;
Molecular Note		A targeting construct was designed to flank exon 12 with loxP sites. This exon is the first to encode the kinase domain. Its excision would result in a frame shift in the ORF, resulting in a null mutation. Western blot confirmed that insertion of the loxP sites did not affect protein expression levels. [MGI Ref ID J:107042]

Genotyping

Genotyping Information

Genotyping Protocols

Braf^tm1Sva, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chen AP; Ohno M; Giese KP; Kuhn R; Chen RL; Silva AJ. 2006. Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory. J Neurosci Res 83(1):28-38. [PubMed: 16342120]  [MGI Ref ID J:107042]

Additional References

Braf^tm1Sva related

Blasco RB; Francoz S; Santamaria D; Canamero M; Dubus P; Charron J; Baccarini M; Barbacid M. 2011. c-Raf, but Not B-Raf, Is Essential for Development of K-Ras Oncogene-Driven Non-Small Cell Lung Carcinoma. Cancer Cell 19(5):652-63. [PubMed: 21514245]  [MGI Ref ID J:172200]

Galabova-Kovacs G; Catalanotti F; Matzen D; Reyes GX; Zezula J; Herbst R; Silva A; Walter I; Baccarini M. 2008. Essential role of B-Raf in oligodendrocyte maturation and myelination during postnatal central nervous system development. J Cell Biol 180(5):947-55. [PubMed: 18332218]  [MGI Ref ID J:136032]

Galabova-Kovacs G; Matzen D; Piazzolla D; Meissl K; Plyushch T; Chen AP; Silva A; Baccarini M. 2006. Essential role of B-Raf in ERK activation during extraembryonic development. Proc Natl Acad Sci U S A 103(5):1325-30. [PubMed: 16432225]  [MGI Ref ID J:105998]

Gerits N; Kostenko S; Moens U. 2007. In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice. Transgenic Res 16(3):281-314. [PubMed: 17219248]  [MGI Ref ID J:122230]

Karreth FA; Frese KK; DeNicola GM; Baccarini M; Tuveson DA. 2011. C-Raf is required for the initiation of lung cancer by K-Ras(G12D). Cancer Discov 1(2):128-36. [PubMed: 22043453]  [MGI Ref ID J:185634]

Newbern J; Zhong J; Wickramasinghe RS; Li X; Wu Y; Samuels I; Cherosky N; Karlo JC; O'Loughlin B; Wikenheiser J; Gargesha M; Doughman YQ; Charron J; Ginty DD; Watanabe M; Saitta SC; Snider WD; Landreth GE. 2008. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A 105(44):17115-20. [PubMed: 18952847]  [MGI Ref ID J:144862]

Provot S; Nachtrab G; Paruch J; Chen AP; Silva A; Kronenberg HM. 2008. A-raf and B-raf are dispensable for normal endochondral bone development, and parathyroid hormone-related peptide suppresses extracellular signal-regulated kinase activation in hypertrophic chondrocytes. Mol Cell Biol 28(1):344-57. [PubMed: 17967876]  [MGI Ref ID J:128917]

Sobczak I; Galabova-Kovacs G; Sadzak I; Kren A; Christofori G; Baccarini M. 2008. B-Raf is required for ERK activation and tumor progression in a mouse model of pancreatic beta-cell carcinogenesis. Oncogene 27(35):4779-87. [PubMed: 18490924]  [MGI Ref ID J:138656]

Tien AC; Tsai HH; Molofsky AV; McMahon M; Foo LC; Kaul A; Dougherty JD; Heintz N; Gutmann DH; Barres BA; Rowitch DH. 2012. Regulated temporal-spatial astrocyte precursor cell proliferation involves BRAF signalling in mammalian spinal cord. Development 139(14):2477-87. [PubMed: 22675209]  [MGI Ref ID J:185602]

Zhong J; Li X; McNamee C; Chen AP; Baccarini M; Snider WD. 2007. Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo. Nat Neurosci 10(5):598-607. [PubMed: 17396120]  [MGI Ref ID J:121660]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous or homozygous mice can be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	002065 129T2/SvEmsJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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