MRL.129X1-Lamc2^jeb/DcrJ

Stock number: 024120
Research areas: Cell Biology Research, Dermatology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This Lamc2^jeb mutant mouse strain may be useful in studies of epidermolysis bullosa and is a model for Non-Herlitz Type Junctional Epidermolysis Bullosa.

Detailed description

The Lamc2 gene encodes for the gamma-2 subunit of laminin 332 (laminin 5), which is an extracellular matrix glycoprotein found in cutaneous basement membranes. These mice carry a spontaneous mutation of Lamc2 that arose on the 129X1 background and is a single retroviral insertion (murine leukemia virus long terminal repeat) in intron 18. Onset of progressive skin blistering disease in homozygotes on the congenic MRL/MpJ background is approximately 8 weeks. Homozygotes exhibit ulcerated lesions and tissue granulation in ear skin, which develops into deformed pinna. Thickened epidermis (hyperplasia) and subepidermal separation, with little to no inflammation, occurs in the skin of the footpads and tail. Due to early onset of phenotype, homozygous crosses rarely produce more than one healthy litter.

Development

The Lamc2^jeb spontaneous mutation arose in the 129X1-Fcgrt^tm1Dcr/Dcr colony of Dr. Derry Roopenian. The mutation was revealed to be a single retroviral insertion (murine leukemia virus long terminal repeat) in intron 18 of the Lamc2 gene. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to MRL/MpJ (Stock No. 000486) for 10 generations. Upon transfer to the Repository the mice were crossed to MRL/MpJ (Stock No. 000486) at least once, to establish the colony.

Allele

Symbol: Lamc2^jeb
Name: junctional epidermolysis bullosa
MGI accession ID: MGI:3609880
Generation method: Spontaneous
Attributes: Hypomorph
Marker symbol: Lamc2
Marker name: laminin, gamma 2
Marker synonyms: B2T; BM600; CSF; EBR2; EBR2A; JEB3A; JEB3B; LAMB2T; LAMNB2; nicein, 100kDa
Chromosome: 1
Strain of origin: 129X1/SvJ
Molecular note: Sequencing of mutant genomic DNA revealed the presence of a single murine leukemia virus long terminal repeat (MLV LTR) insertion of 560 bp within the eighteenth intron. Northern blot and RT-PCR analysis detected an aberrant transcript that retains intron 18 and the LTR, and introduces a TAG translational stop codon in intron 18. However, a correctly spliced WT transcript is also produced at low abundance suggesting that this allele acts as a hypomorph. A noncomplementation test with a null allele of this gene further confirmed that the insertion is the cause of the mutant phenotype.