Fbn1Tsk homozygotes are embryonic lethal; heterozygotes exhibit excessive growth and hyperplasia of connective tissue, cartilage, tendon sheaths and bone. This strain is a model for Marfan Syndrome, Hereditary Pulmonary Emphysema, Stiff Skin Syndrome and Familial Progressive Scleroderma.
IMR Colony, The Jackson Laboratory
The Fbn1Tsk allele contains a 30 to 40 kbp genomic tandem duplication resulting in a larger than normal in-frame transcript. Homozygotes are embryonic lethal, failing to survive past somite formation (7-8 days of gestation). Heterozygotes are viable and fertile, exhibiting excessive growth and hyperplasia of connective tissue, cartilage, tendon sheaths and bone. Skin tightness, due to hyperplasic thickening of subcutaneous loose connective tissue and abnormal organization and distribution of skin microfibrillar arrays, develops by the first week after birth. Although the size of the skeleton is increased, body weight remains normal. Mutant mice exhibit polyuria during the light cycle. Collagens and glycosaminoglycans accumulate in the skin, heart, lungs and bladder. Hypertrophy is also observed in the enlarged heart (aortic adventitia). Mutant mice have enlarged thoracic size and lungs with abnormal alveolar walls, irregular shaped alveoli, and increased lung capacity. By 1 month of age, heterozygotes develop emphysema with progressive destruction of alveolar walls and loss of elasticity. Inflammatory macrophages and neutrophils infiltrate the lower respiratory tract. The abnormal immune system characteristics exhibited by this strain also include: alveolitis, increased number of mast cells in the skin, presence of autoantibodies specific for scleroderma target antigens and anti-nuclear antibodies.
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. This is the case for the strain above. 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.
The spontaneous mutation Fbn1Tsk (tight skin) arose in 1977 at The Jackson Laboratory from the B10.D2(58N) congenic resistant strain.
This strain was generated by breeding B6.Cg-Fbn1Tsk +/+ Bloc1s6pa/J (Stock No. 000305) to C57BL6/J (Stock No. 000664) to remove the Bloc1s6pa allele.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||tight skin|
|Gene Symbol and Name||Fbn1, fibrillin 1|
|Strain of Origin||B10.D2/(58N)Sn|
|General Note||Genbank ID for this allele: AF007248|
|Molecular Note||This allele harbors a 30 to 40kb genomic tandem duplication within the Fbn1 gene that results in a larger than normal in-frame transcript produced at normal levels.|
Homozygotes are not viable. When maintaining a live colony, C57BL/6J female mice may be bred with heterozygous male mice.
When using the B6-tight skin mouse strain in a publication, please cite the originating article(s) and include JAX stock #014632 in your Materials and Methods section.