Strain Detail Sheet

Strain Name    :

B6.Cg-Myo5aflr Gnb5flr/Mmnc

Stock Number :

000070-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Myo5aflr
Name: flailer
Chromosome: 9; 42.0 cM
Alteration at locus: Spontaneous Mutation
Allele Symbol: Gnb5flr
Name: flailer
Chromosome: 9; 41.0 cM
Alteration at locus: Spontaneous Mutation
Gene Symbol: Myo5a
Name: myosin VA
Chromosome: 9
Alteration at locus: Spontaneous Mutation
Gene Symbol: Gnb5
Name: guanine nucleotide binding protein (G protein), beta 5
Chromosome: 9
Alteration at locus: Spontaneous Mutation

Genetic Alterations:
Due to unequal recombination within an intron of the two affected genes, the mutant chromosome contains an extra hybrid gene in addition to wildtype copies of Gnb5 and Myo5a. The flailer mice produce a hybrid protein containing the cargo-binding domain of Myosin 5a, which is expressed in neurons only. The hybrid protein acts as a dominant negative inhibitor of transport processes dependent on Myo5a.

Genotype Determination:

ES Cell Line: Not Applicable

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Neurological abnormalities by 14 days postnatal include frequent falling, convulsive limb movements, opisthotonos in response to handling. Unlike the Myo5a-neurological mutants which it resembles at 2-4 weeks of age, flailer mice recover and exhibit only mild ataxia as adults. Adults do not perform well on rotorod. The histological phenotype includes delayed localization of smooth ER in dendritic spines of cerebellar Purkinje cells.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Myo5aflr/Myo5aflr
        involves: C57BL/6J * C57BL/10J * CBA/Ca
  • mortality/aging
    • postnatal lethality (MGI Ref ID J:42513)
      • 50% of animals survive only 3 weeks; lethality may be partially background-sensitive
  • behavior/neurological phenotype
    • abnormal motor capabilities/coordination/movement (MGI Ref IDs J:61324, J:42513)
      • by 14 days of age, mice exhibit frequent falling behavior (MGI Ref ID J:61324)
      • frequent falls exhibited by 50% of mice (MGI Ref ID J:42513)
      • ataxia (MGI Ref ID J:61324)
        • adults display mild ataxia
      • ataxia (MGI Ref ID J:42513)
        • 50% of homozygotes are severely ataxic
        • other 50% show transient ataxia at 3 weeks of age
      • impaired balance (MGI Ref ID J:61324)
        • adults cannot maintain balance on a narrow beam
      • impaired coordination (MGI Ref ID J:61324)
        • mice fall off rotating rod within 0.5-1 minute; coordination improves with age
      • impaired righting response (MGI Ref IDs J:61324, J:42513)
        • by 14 days of age, mi ce display convulsive limb movements during attempts to right themselves (MGI Ref ID J:61324)
        • legs flail during attempts to right themselves in 50% of animals (MGI Ref ID J:42513)
      • opisthotonus (MGI Ref ID J:61324)
        • can be stimulated by handling between 2 and 4 weeks of age
    • convulsive seizures (MGI Ref ID J:61324)
      • increase in frequency between 2 and 4 weeks of age
  • nervous system phenotype
    • abnormal cerebellum morphology (MGI Ref ID J:61324)
      • localization of smooth endoplasmic reticulum (SER) vesicles is abnormal in cerebellum of 20-day old mice
      • abnormal Purkinje cell dendrite morphology (MGI Ref ID J:61324)
        • Times New Roman
    • convulsive seizures (MGI Ref ID J:61324)
      • increase in frequency between 2 and 4 weeks of age
  • muscle phenotype
    • opisthotonus (MGI Ref ID J:61324)
      • can be stimulated by handling between 2 and 4 weeks of age
  • pigmentation phenotype
    • pigmentation phenotype (MGI Ref ID J:61324)
      • mutants have normal pigment indicating C-terminus exons of Myo5a are not involved in the dilute coat color change associated with other Myo5a mutations

Strain of Origin: C57BL/10J, CBA

Strain genetic background: C57BL/6J

Strain Development: B6CBACa-AWJ/A, tb2J/tb2J F2 mice were obtained from the frozen embryo repository at the Jackson Laboratory (Bar Harbor, ME). These mice were backcrossed once to strain C57BL/6J and heterozygous flr/+ offspring were intercrossed. flailer has subsequently been maintained by brother–sister mating of homozygous affected animals. The resulting recombinant congenic line, STOCK Myo5aflr Gnb5flr/Unc, was sib mated for at least10 generations. The composition of the background stock was ~75% C57BL/6J and 25% CBA prior to backcrossing to C57BL/6 (N>10).

Suggested Control Mice:

  • C57BL/6

Research Applications

  • Neurologic. Can be used to study Myo5a dependent processes.

Strain Origin

Donor: Miriam Meisler, Ph.D., University of Michigan

Primary Reference:

Jones JM, Huang JD, Mermall V, Hamilton BA, Mooseker MS, Escayg A, Copeland NG, Jenkins NA, Meisler MH. The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a. Hum Mol Genet. 2000 Mar 22;9(5):821-8. (Medline PMID: 10749990)

Colony and Husbandry Information

Special Considerations

Careful handling during cage changing, avoid noise, mice may go into convulsions from which they will recover.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.

Appearance

Coat color: Agouti

Other:

Breeding

MMRRC Breeding System: Sib matings

Breeding Scheme(s):

  • Homozygous female x Homozygous male
    Heterozygous female x Heterozygous male
     

Generation: N10+ As of: 5/2002

Overall Breeding Performance: Slow, small litters

Breeding Comments: Homozygous mice exhibit limb convulsions between 2-4 weeks of age, phenotype tends to lessen as mice age.

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: 4 to 6

Recommended wean age: 4 weeks - do not wean earlier due to neurological phenotype

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
000070-UNC-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
Litter Recovered litter1; additional fees for any special requests.

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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