Overview

The Flnc Δ41-48 mutant allele has the last eight exons (exons 41-48) of the filamin C (FLNc) locus deleted. The Flnc Δ41-48 mutant mice may be useful in studying muscle physiology, primary myogenesis, muscle differentiation, and maintenance of elongated muscle fiber structure in the sarcomere.

Donating Investigator

Louis M Kunkel, Children's Hospital Boston

Genetic overview

Genetic Background	Generation

Flnc^tm1Lmk

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Flnc	filamin C, gamma

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Research Applications

Developmental Biology Research
Research Tools
Cell Biology Research
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Flnc Δ41-48 mutant allele has the last eight exons (exons 41-48) of the filamin C (FLNc) locus deleted. The deleted region encodes the last five filamin-like repeats (including the dimerization domain) and the Hinge 2 domain of FLNc. As such, the Flnc Δ41-48 allele expresses a truncated mRNA at reduced levels compared to the wildtype allele in limb muscle and heart tissues. Western blot analysis on limb muscle protein lysates shows that the Flnc Δ41-48 allele expresses a truncated protein at very low levels. Heterozygous mice are viable and fertile with no reported abnormalities. Mice homozygous for the Flnc Δ41-48 allele die at birth. At embryonic day (E)18.5, homozygous mice born via Cesarean section are able to take several short breaths but exhibit respiratory distress (failure to inflate lungs) and die shortly thereafter. While the hearts of the homozygotes appear normal and unaffected, skeletal muscles exhibit severe abnormalities including muscle fibers with centrally located nuclei and infiltration of connective tissue, especially in intercostal and diaphragm muscles. Decreased muscle mass and defects in primary myogenesis are also observed in several skeletal muscle groups (including trunk, limb, intercostal, tongue, extraocular, and facial muscles).

Development

A targeting vector was designed to replace the last eight exons of the filamin C (FLNc) locus with a loxP-flanked neomycin resistance gene. The deleted ~4.5 kb region spans exons 41-48 that encode the last five filamin-like repeats (including the dimerization domain) and the Hinge 2 domain of FLNc. The targeting construct was electroporated into 129SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6J mice to establish the colony. Mice heterozygous for the Flnc Δ41-48 allele were backcrossed to C57BL/6J mice and/or wildtype mice from the colony for several generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Dalkilic I; Schienda J; Thompson TG; Kunkel LM. 2006. Loss of FilaminC (FLNc) results in severe defects in myogenesis and myotube structure. Mol Cell Biol 26(17):6522-34PubMed: 16914736 MGI: J:112170

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Genetics

Flnc^tm1Lmk

Allele Symbol: Flnc^tm1Lmk

Allele Name	targeted mutation 1, Louis M Kunkel
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Flnc, filamin C, gamma
Gene Synonym(s)
Strain of Origin	129
Chromosome	6
Molecular Note	A loxP-flanked neomycin selection cassette replaced 4.1kb of the gene, including the last eight exons (41-48). Western blot analysis on muscle lysates derived from homozygous mice indicated that a truncated protein is expressed at low levels from this allele.
Mutations Made By	Louis Kunkel, Children's Hospital Boston

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Internal/Organ Defects
  - multiple
- Mesodermal Defects
  - Myogenesis Defects
- Perinatal Lethality
  - Homozygous
Research Tools
- Developmental Biology Research
- Genetics Research
  - Mutagenesis and Transgenesis: transcriptional activation
Cell Biology Research
- Signal Transduction
- Transcriptional Regulation
Immunology, Inflammation and Autoimmunity Research
- Intracellular Signaling Molecules

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Flnc^tm1Lmk/Flnc^tm1Lmk
involves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

hyporesponsive to tactile stimuli

growth/size/body region phenotype

decreased fetal size
- body weight is similar to wild-type at E16.5 but significantly reduced just before birth
- correlates with reduction in muscle mass

respiratory system phenotype

respiratory failure
- lungs of newborns are not inflated

integument phenotype

hyporesponsive to tactile stimuli

mammalian phenotype

cardiovascular system phenotype
- Normal - heart morphology is similar to wild-type

mortality/aging

neonatal lethality, complete penetrance
- all die at birth
- homozygotes born by cesarean section at E18.5 die after taking only a few short breaths

muscle phenotype

abnormal diaphragm morphology
- fibers with centrally located nuclei and infiltration of connective tissue are seen
- less severe than in the intercostal muscle

abnormal extensor digitorum longus morphology
- reduced number of overall muscle fibers as well as primary muscle fibers

abnormal intercostal muscle morphology
- fibers with centrally located nuclei and infiltration of connective tissue are seen

abnormal myogenesis
- significant reduction in the number of primary muscle fibers in the soleus, tibialis anterior, and extensor digitorum longus muscles

abnormal skeletal muscle fiber morphology
- rounded fibers with centrally located nuclei are seen; however, no increase in the number of apoptotic fibers is detected
- sarcomeric structure is disorganized in the rounded fibers

abnormal skeletal muscle morphology
- infiltration of connective tissue especially in muscles responsible for respiration

abnormal soleus morphology
- reduced number of overall muscle fibers as well as primary muscle fibers

abnormal tibialis anterior morphology
- reduced number of overall muscle fibers as well as primary muscle fibers

centrally nucleated skeletal muscle fibers
- fibers with centrally located nuclei are seen in the diaphragm and the intercostals muscles
- occurrence of large fibers with centrally located nuclei is seen in some muscles

decreased skeletal muscle fiber number
- reduced fiber number seen in various skeletal muscles

decreased skeletal muscle mass
- muscle mass is decreased in trunk, limb, intercostal, tongue, extraocular, and facial muscles

increased variability of skeletal muscle fiber size
- increased variability in fiber diameter

References

Dalkilic I; Schienda J; Thompson TG; Kunkel LM. 2006. Loss of FilaminC (FLNc) results in severe defects in myogenesis and myotube structure. Mol Cell Biol 26(17):6522-34PubMed: 16914736 MGI: J:112170

Additional - Flnc^tm1Lmk related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Flnc
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred with wildtype mice from the colony or with C57BL/6J inbred mice (Stock No. 000664). Mice homozygous for the Flnc Δ41-48 allele die at birth.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129-Flnc^tm1Lmk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014125 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Flnc<tm1Lmk>

Related Products and Services

Frozen Mouse Embryo	B6;129-Flnc<tm1Lmk>/J	$2595.00
Frozen Mouse Embryo	B6;129-Flnc<tm1Lmk>/J	$2595.00
Frozen Mouse Embryo	B6;129-Flnc<tm1Lmk>/J	$3373.50
Frozen Mouse Embryo	B6;129-Flnc<tm1Lmk>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Flnctm1Lmk

Allele Symbol: Flnctm1Lmk

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Flnctm1Lmk/Flnctm1Lmkinvolves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

respiratory system phenotype

integument phenotype

mammalian phenotype

mortality/aging

muscle phenotype

References

Additional - Flnctm1Lmk related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Flnc^tm1Lmk

Allele Symbol: Flnc^tm1Lmk

Genotype: Flnc^tm1Lmk/Flnc^tm1Lmk
involves: 129X1/SvJ * C57BL/6

Additional - Flnc^tm1Lmk related