Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Heterozygote         (Female x Male)   25-MAY-12 Species laboratory mouse Generation N6pN1+ Generation Definitions   Donating Investigator Douglas Black,   UCLA

Description
These Fox-2^flox mutant mice possess loxP sites flanking exons 6-7 of the RNA binding protein, fox-1 homolog 2 (Rbfox2) gene. Mice that are homozygous for this allele are viable, fertile, and normal in size. Fox-2 is widely expressed, highest in brain and heart, 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 6-7 deleted in the Cre-expressing tissue, resulting in inactivation of Fox-2 gene function.

When bred to mice carrying Tg(Pcp2-cre)2Mpin (Stock No. 004146) and Rbfox1^tm1.1Dblk (Stock No. 014089) , 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 6-7 of the RNA binding protein, fox-1 homolog 2 (Rbfox2) 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 transiently transfected with a pTurboCre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 6-7, intact floxed-neo cassette, or excision of both exons 6-7 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exons 6-7, were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. These mice were backcrossed to C57BL/6J mice for at least 6 generations resulting in a colony of Fox-2^flox mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	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^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)

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

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

• mortality/aging
• partial lethality
  • mice that develop hydrocephalus require euthanasia   (MGI Ref ID J:181631)
• partial postnatal lethality
  • about 40% of males die by 1 month of age   (MGI Ref ID J:181631)
• nervous system phenotype
• abnormal neuron physiology
  • Purkinje cells show a moderate decrease in firing frequency   (MGI Ref ID J:181631)
• • abnormal Purkinje cell migration
    • at E18 many Purkinje cells remain near their origin in the ventricular zone   (MGI Ref ID J:181631)
  • abnormal cerebellar granule cell proliferation
    • minor decrease in proliferation in the external granule cell layer   (MGI Ref ID J:181631)
    • marked reduction in proliferation in the internal granule cell layer   (MGI Ref ID J:181631)
  • increased neuron apoptosis
    • three fold increase in apoptosis per unit are at P5 in the cerebellum   (MGI Ref ID J:181631)
• ectopic Purkinje cell
  • more than 10% of the Purkinje cells are ectopically located in the internal granule cell layer at P10   (MGI Ref ID J:181631)
• hydroencephaly
  • some surviving mice (12 of 33) develop hydrocephalus at 8 - 12 weeks of age   (MGI Ref ID J:181631)
• increased Purkinje cell number
  • about 20% more Purkinje cells per unit area at P5 in the cerebellum   (MGI Ref ID J:181631)
  • however, at later stages cell numbers do not differ   (MGI Ref ID J:181631)
• small cerebellum   (MGI Ref ID J:181631)
• thin cerebellar molecular layer
  • at P10   (MGI Ref ID J:181631)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • mice exhibit normal susceptibility to spontaneous or induced seizures   (MGI Ref ID J:176189)
• • abnormal locomotor activation
    • impaired locomotion that worsens with age   (MGI Ref ID J:181631)
  • abnormal posture
    • worsens with age   (MGI Ref ID J:181631)
• growth/size phenotype
• decreased body weight
  • males weigh only 44% of wild-type males at P21   (MGI Ref ID J:181631)
  • females weigh only 59% of wild-type females at P21   (MGI Ref ID J:181631)
• cellular phenotype
• abnormal Purkinje cell migration
  • at E18 many Purkinje cells remain near their origin in the ventricular zone   (MGI Ref ID J:181631)
• abnormal cerebellar granule cell proliferation
  • minor decrease in proliferation in the external granule cell layer   (MGI Ref ID J:181631)
  • marked reduction in proliferation in the internal granule cell layer   (MGI Ref ID J:181631)
• increased neuron apoptosis
  • three fold increase in apoptosis per unit are at P5 in the cerebellum   (MGI Ref ID J:181631)

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		Rbfox2tm1.1Dblk
Allele Name		targeted mutation 1.1, Douglas Black
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Fox-2flox; Rbfox2loxP;
Mutation Made By		Douglas Black,   UCLA
Strain of Origin		129S2/SvPas
Gene Symbol and Name		Rbfox2, RNA binding protein, fox-1 homolog (C. elegans) 2
Chromosome		15
Gene Common Name(s)		2810460A15Rik; AA407676; AI118529; FOX2; Fbm2; Fox-2; Fxh; Fyn-binding molecule 2; HNRBP2; HRNBP2; RBM9; RIKEN cDNA 2810460A15 gene; RNA binding motif protein 9; RTA; Rbm9; dJ106I20.3; expressed sequence AA407676; expressed sequence AI118529; fox-1 homolog (C. elegans);
Molecular Note		A targeting vector was designed to insert loxP sites flanking exons 6-7 of the RNA binding protein, fox-1 homolog 2 (Rbfox2) gene, followed by a FRT-flanked neomycin resistance (neo) cassette. Flp-mediated recombination removed the neo cassette and left exons 6 and 7 floxed. [MGI Ref ID J:165699]

Genotyping

Genotyping Information

Genotyping Protocols

Rbfox2^tm1.1Dblk, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Rbfox2^tm1.1Dblk related

Black D. 2010. Direct Data Submission 2010/11/09 MGI Direct Data Submission :.  [MGI Ref ID J:165699]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Heterozygote x Heterozygote         (Female x Male)   25-MAY-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.