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.
Louis M Kunkel, Children's Hospital Boston
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).
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.
|Allele Name||targeted mutation 1, Louis M Kunkel|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Flnc, filamin C, gamma|
|Strain of Origin||129|
|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
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.
When using the B6;129-Flnctm1Lmk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014125 in your Materials and Methods section.