129X1/SvJ-Lamc2^jeb/DcrJ

Stock number: 006859
Research areas: Cell Biology Research, Dermatology Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research

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

Mice that are heterozygous for this mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Northern blot analysis of skin from homozygotes detects the wildtype and a dominant larger sized mutant gene product (mRNA). Homozygotes express a reduced level of gene product (protein), as detected by Western blot analysis of keratinocytes. Mean onset of progressive skin blistering disease in homozygotes on the 129X1 background is age 154 days. Homozygotes exhibit ulcerated lesions and tissue granulation in ear skin, which develops into deformed pinna; ulcerated lesions in the footpads and tail. Thickened epidermis (hyperplasia) and subepidermal separation, with little to no inflammation, occurs in the skin of the footpads and tail. Ultrastructural analysis of skin with electron microscopy reveals that the dermal-epidermal separation occurs at the lamina lucida.

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.

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
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.