B6.129S1(Cg)-Lmna^tm1Stw/BkknJ

Stock number: 009125
Product name: lamin A/C , Lmna -/-
Research areas: Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

Mice harboring the lamin A/C (Lmna) null mutation are a model for the autosomal variant of Emery-Dreifuss muscular dystrophy (EDMD) and may be useful in studying the role of lamins, inner nuclear membrane proteins, nuclear envelope integrity, and chromatin domain anchoring sites in EDMD.

Detailed description

Mice heterozygotes for this lamin A/C mutation are viable and fertile. The targeted allele does not express both full-length transcripts or stable lamin A/C protein. Homozygotes (Lmna -/- mice) exhibit severely retarded postnatal growth beginning as early as 2 weeks of age and abnormal movement/gait by 3-4 weeks of age that progresses to distinct scoliosis/kyphosis and death around 8 weeks of age. Lmna -/- mice also have tissue-specific alterations of nuclear envelope integrity and mislocalization of the inner nuclear membrane protein emerin. In skeletal and cardiac muscle, this results in rapid myopathic onset closely resembling Emery-Dreifuss muscular dystrophy (EDMD). These mice are a model for the autosomal variant of EDMD and may be useful in studying the role of lamins, inner nuclear membrane proteins, nuclear envelope integrity, and chromatin domain anchoring sites in EDMD.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

These lamin A/C-mutant mice were published in 1999 and generated by the laboratory of Dr. Colin L. Stewart (National Cancer Institute-Frederick Cancer Research and Development Center, Maryland). A targeting vector was designed to replace exon 8 through part of exon 11 of the lamin A/C (Lmna) locus with a reverse-oriented PGK-neomycin resistance cassette. This removed 114 codons as well as the 3' UTR, including the polyadenylation signal of lamin C, whereas 152 codons were eliminated from the lamin A coding region. The targeting construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and the resulting mutant mice were maintained on an undisclosed genetic background. In 2006, Lmna-mutant mice were sent to the laboratory of Brian K. Kennedy (University of Washington, Seattle) where they were subsequently backcrossed to C57BL/6J inbred mice for at least nine generations prior to sending to The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the mutant colony. The Y chromosome may not have been fixed to the genetic background during the backcross.

Allele

Symbol: Lmna^tm1Stw
Name: targeted mutation 1, Colin L Stewart
MGI accession ID: MGI:2177930
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Lmna-
Marker symbol: Lmna
Marker name: lamin A
Marker synonyms: CDCD1; CDDC; CMD1A; CMT2B1; Dhe; EMD2; FPL; FPLD; FPLD2; HGPS; IDC; lamin A/C; LDP1; LFP; LGMD1B; LMN1; LMNC; LMNL1; MADA; PRO1
Chromosome: 3
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: A PGK-neomycin resistance cassette replaced a genomic segment containing exons 8-10. Western blot analysis on extracts of both embryonic fibroblasts and liver nuclear membranes from homozygous mice confirmed that no detectable protein was expressed from this allele.