These mice carry a W1572C mutation in the mouse Fbn1 gene and serve as a model of human stiff skin syndrome with increased collagen deposition in the dermis, decreased subcutaneous fat, and circulating anti-nuclear and anti-topoisomerase I antibodies.
Harry Dietz, Johns Hopkins Medical Institute
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Humanized sequence) | Fbn1 | fibrillin 1 |
Stiff skin syndrome (SSS), a form of scleroderma defined by a pathological fibrosis of the skin, is caused by heterozygous missense mutations in the Arg-Gly-Asp (RGD) integrin-binding domain of the FBN1 (fibrillin 1) gene.
These mice carry a W1572C mutation (equivalent of the human W1570C mutation) in the mouse Fbn1 gene. The mutation is widely expressed in tissues including the skin, aorta, lungs and liver. Heterozygotes serve as a model of human stiff skin syndrome with increased collagen deposition in the dermis by 1 month of age, decreased subcutaneous fat by 3 months of age, disorganized and excessive microfibrillar aggregates in the dermis, and circulating anti-nuclear and anti-topoisomerase I antibodies by three months of age. Mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells, and plasma cells. Mice homozygous for the W1572C mutation are viable and show accelerated skin fibrosis when compared with heterozygous littermates.
Site-directed mutagenesis was used to create a W1572C mutation (equivalent of the human W1570C mutation) in exon 38 of the targeted gene. A loxP-flanked neomycin resistance cassette was placed upstream in intron 37. The targeting vector was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells and the resultant chimeric mice were bred to C57BL/6J animals. The floxed neomycin cassette was excised through crosses with an EIIa-Cre strain (see Stock No. 003724). This strain was backcrossed to C57BL/6J for 4 generations by the donating laboratory (see SNP note below).
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. Eight of the 27 markers throughout the genome were segregating, suggested an in complete backcross. Three 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 | targeted mutation 3.1, Harry C Dietz |
---|---|
Allele Type | Targeted (Humanized sequence) |
Allele Synonym(s) | Fbn1W1572C |
Gene Symbol and Name | Fbn1, fibrillin 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 2 |
Molecular Note | Exon 38 was replaced with a floxed neomycin resistance cassette and a modified exon 38 in which nucleotide substitutions result in the amino acid substitution of cysteine for tryptophan at position 1572 (W1572C). This mutation is associated with stiff skin syndrome (SSS) in human patients. Cre-mediated recombination removed the selection cassette. |
Heterozygotes are viable and fertile. Homozygous fertility is reduced slightly in males, more so in females.
When using the STOCK Fbn1tm3.1Hcd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025474 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Fbn1<tm3.1Hcd> |
Frozen Mouse Embryo | STOCK Fbn1<tm3.1Hcd>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Fbn1<tm3.1Hcd>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Fbn1<tm3.1Hcd>/J | $3373.50 |
Frozen Mouse Embryo | STOCK Fbn1<tm3.1Hcd>/J | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.