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 N6pN1 Generation Definitions   Donating Investigator Douglas Black,   UCLA

Description
These Fox1^flox mutant mice possess loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene. Mice that are homozygous for this allele are viable, fertile, and normal in size. Fox-1 is expressed in brain, heart, and skeletal muscle and regulates alternative splicing in vertebrates by binding specifically to (U)GCAUG sequences. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exons 11-12 deleted in the Cre-expressing tissue, resulting in inactivation of Fox-1 gene function.

For example, when crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of neuronal excitation and seizures.

When bred to mice carrying Tg(Pcp2-cre)2Mpin (Stock No. 004146) and Rbfox2^tm1.1Dblk (Stock No. 014090) , Cre recombinase expression in the Purkinje cells may be useful in studies of Purkinje cell pacemaking.

Development
A targeting vector was designed to insert loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene, followed by a frt-flanked neomycin resistance (neo) cassette. The construct was electroporated into 129S2/Sv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J transgenic mice (Stock No. 003946) to delete the neo cassette, resulting in a colony of Fox-1^flox mice. The donating investigator reported that the resulting offspring were then backcrossed to C57BL/6J mice for at least 6 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 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	(approximate)
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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.

Rbfox1^tm1.1Dblk/Rbfox1⁺ Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk Tg(Nes-cre)1Kln/0

        involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL   (conditional)

• mortality/aging
• complete postnatal lethality
  • euthanasia due to immobility by 3?4 weeks of age   (MGI Ref ID J:181631)
• nervous system phenotype
• abnormal neuron physiology
  • Purkinje cells show a marked decrease in firing frequency   (MGI Ref ID J:181631)
• ectopic Purkinje cell   (MGI Ref ID J:181631)
• small cerebellum   (MGI Ref ID J:181631)
• behavior/neurological phenotype
• ataxia
  • develop severe ataxia by 2 weeks of age becoming immobile by 3-4 weeks of age   (MGI Ref ID J:181631)
• growth/size phenotype
• decreased body size
  • very small   (MGI Ref ID J:181631)

Rbfox1^tm1.1Dblk/Rbfox1⁺ Tg(Nes-cre)1Kln/0

        involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL   (conditional)

• mortality/aging
• increased sensitivity to xenobiotic induced morbidity/mortality
  • in mice treated with kainic acid   (MGI Ref ID J:176189)
• nervous system phenotype
• increased susceptibility to pharmacologically induced seizures
  • increased incidence resulting in death in response to kainic acid treatment   (MGI Ref ID J:176189)
• behavior/neurological phenotype
• increased susceptibility to pharmacologically induced seizures
  • increased incidence resulting in death in response to kainic acid treatment   (MGI Ref ID J:176189)
• homeostasis/metabolism phenotype
• increased sensitivity to xenobiotic induced morbidity/mortality
  • in mice treated with kainic acid   (MGI Ref ID J:176189)

Rbfox1^tm1.1Dblk/Rbfox1^tm1.1Dblk Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk Tg(Nes-cre)1Kln/0

        involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL   (conditional)

• mortality/aging
• complete perinatal lethality   (MGI Ref ID J:181631)

Rbfox1^tm1.1Dblk/Rbfox1^tm1.1Dblk Rbfox2^tm1.1Dblk/Rbfox2^tm1.1Dblk Tg(Pcp2-cre)2Mpin/0

        involves: 129 * C57BL/6J   (conditional)

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • do not display ataxia   (MGI Ref ID J:181631)
• • impaired coordination
    • shorter mean latency to fall in the first trial and performance improves only slightly over subsequent trials   (MGI Ref ID J:181631)
• nervous system phenotype
• *normal* nervous system phenotype
  • do not display defects in cerebellar development   (MGI Ref ID J:181631)
• • abnormal neuron physiology
    • at P70, but not at P20, Purkinje cells show a decrease in firing frequency   (MGI Ref ID J:181631)
    • at P70 Purkinje cells show an increase in variability of firing   (MGI Ref ID J:181631)

Rbfox1^tm1.1Dblk/Rbfox1^tm1.1Dblk Tg(Nes-cre)1Kln/0

        involves: 129S2/SvPas * 129S4/SvJaeSor * C57BL/6 * C57BL/6J * SJL   (conditional)

• mortality/aging
• increased sensitivity to xenobiotic induced morbidity/mortality
  • in mice treated with kainic acid   (MGI Ref ID J:176189)
• reproductive system phenotype
• reduced fertility   (MGI Ref ID J:176189)
• nervous system phenotype
• *normal* nervous system phenotype
  • mice exhibit normal gross brain morphology   (MGI Ref ID J:176189)
• • abnormal dendritic spine morphology
    • very modest decrease in spine density in the dentate gyrus   (MGI Ref ID J:176189)
  • abnormal excitatory postsynaptic potential
    • mice require lower stimulus intensities to evoke field excitatory postsynaptic potentials compared with control mice   (MGI Ref ID J:176189)
  • seizures
    • infrequent spontaneous seizures   (MGI Ref ID J:176189)
  • • increased susceptibility to pharmacologically induced seizures
      • increased incidence and duration of tonic-clonic seizures resulting in death in response to kainic acid treatment   (MGI Ref ID J:176189)
    • tonic-clonic seizures
      • in mice treated with kainic acid   (MGI Ref ID J:176189)
• growth/size phenotype
• decreased body size
  • slightly   (MGI Ref ID J:176189)
• behavior/neurological phenotype
• seizures
  • infrequent spontaneous seizures   (MGI Ref ID J:176189)
• • increased susceptibility to pharmacologically induced seizures
    • increased incidence and duration of tonic-clonic seizures resulting in death in response to kainic acid treatment   (MGI Ref ID J:176189)
  • tonic-clonic seizures
    • in mice treated with kainic acid   (MGI Ref ID J:176189)
• homeostasis/metabolism phenotype
• increased sensitivity to xenobiotic induced morbidity/mortality
  • in mice treated with kainic acid   (MGI Ref ID J:176189)

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      brain
      heart

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Rbfox1tm1.1Dblk
Allele Name		targeted mutation 1.1, Douglas Black
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Fox-1flox; Rbfox1loxP;
Mutation Made By		Douglas Black,   UCLA
Strain of Origin		129S2/SvPas
Gene Symbol and Name		Rbfox1, RNA binding protein, fox-1 homolog (C. elegans) 1
Chromosome		16
Gene Common Name(s)		2BP1; A2BP1; A2bp; A2bp1; FOX-1; FOX1; HRNBP1; ataxin 2 binding protein 1;
Molecular Note		A targeting vector was designed to insert loxP sites flanking exons 11-12 of the RNA binding protein, fox-1 homolog 1 (Rbfox1) gene, followed by a frt-flanked neomycin resistance (neo) cassette. Flp-mediated recombination removed the neo cassette leavingexons 11 and 12 floxed. [MGI Ref ID J:165698]

Genotyping

Genotyping Information

Genotyping Protocols

Rbfox1^tm1.1Dblk, Melt Curve Analysis
Rbfox1^tm1.1Dblk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Black D. 2010. Direct Data Submission 2010/11/09 MGI Direct Data Submission :.  [MGI Ref ID J:165698]

Additional References

Rbfox1^tm1.1Dblk related

Gehman LT; Meera P; Stoilov P; Shiue L; O'Brien JE; Meisler MH; Ares M Jr; Otis TS; Black DL. 2012. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function. Genes Dev 26(5):445-60. [PubMed: 22357600]  [MGI Ref ID J:181631]

Gehman LT; Stoilov P; Maguire J; Damianov A; Lin CH; Shiue L; Ares M Jr; Mody I; Black DL. 2011. The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain. Nat Genet 43(7):706-11. [PubMed: 21623373]  [MGI Ref ID J:176189]

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, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
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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