| |||||||
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote (Female x Male) Species laboratory mouse Generation N10+N3F1 (03-DEC-07) Donating Investigator Francesco Ramirez, UMDNJ-Robert Wood Johnson Med Sch Description
Both heterozygous and homozygous "mgR" mutant mice are viable with no phenotypic abnormalities at birth. The protein expressed from this mutant allele is the same size as wild-type. Skin tissues show an intermediate reduction in transcript levels compared to wild-type and the mg-delta null allele. Thus the "mgR" mutation does not completely ablate gene function (resulting in rapid death). Instead, expression is hypomorphic and conducive to studying the clinical stages precursive to animal lethality. Homozygotes develop medial calcification, the inflammatory-fibroproliferative response, and inflammation-mediated elastolysis in the natural history of dissecting aneurysm and die between 2-6 month of age with Marfan syndrome (MFS)-like manifestations.Development
A targeting vector containing a PGKneo cassette was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. An unequal crossover event inserted the PGKneo-cassette between exons 18 and 19 of the endogenous gene, resulting in no loss of endogenous sequence for this "mgR" mutant allele. Interestingly, a 67 bp long A/T-rich stretch of DNA was found to have been added at the point of transition between introns 24 and 18. Targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimera's were bred to C57BL/6 mice to establish heterozygous mutants. Heterozygotes were backcrossed to C57BL/6 mice for 10 generations and then maintained by breeding heterozygotes together for many generations prior to arrival at The Jackson Laboratory.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Fbn1
000305 B6.Cg-Fbn1Tsk +/+ Pldnpa/J View Strains carrying other alleles of Fbn1 (1 strain)
Congenic Nomenclature
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Marfan Syndrome; MFS - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Fbn1tm2Rmz/Fbn1tm2Rmz
involves: 129S1/Sv * 129X1/SvJ
- life span-post-weaning/aging
- premature death (MGI Ref ID J:54081)
- die at an average age of 3.8 +/- 3.4 months
- cardiovascular system phenotype
- abnormal vasculature (MGI Ref ID J:54081)
- loss of structural integrity of vessel wall
- newborns exhibit normal vasculature however with age develop late-onset vascular disease
- abnormal aorta morphology (MGI Ref ID J:54081)
- 9 of 20 exhibit medial necrosis and vasculitis
- 8 of 20 exhibit medial calcification
- 6 of 20 exhibit intimal hyperplasia
- 12 of 20 exhibit adventitia hyperplasia with inflammation
- aortic elastic tissue lesions (MGI Ref ID J:54081)
- arterial calcification (MGI Ref ID J:54081)
- calcification of intact elastic lamellae in the aorta is seen as early as 6 weeks of age
- calcified segments increase in frequency and coalesce over time
- aneurysm (MGI Ref ID J:54081)
- in the most advanced aneurysms, an infiltrate of macrophages is found at the adventitial surface with extension into an obliterated tunica media
- hemorrhage (MGI Ref ID J:54081)
- hemomediastinum
- vasculitis (MGI Ref ID J:54081)
- 9 of 20 exhibit medial aorta vasculitis
- respiratory system phenotype
- hemothorax (MGI Ref ID J:54081)
- respiratory distress (MGI Ref ID J:54081)
- mice with kyphosis and diaphragmatic hernia exhibit respiratory distress
- skeleton phenotype
- abnormal rib morphology (MGI Ref ID J:54081)
- dramatic overgrowth of the ribs
- increased length of long bones (MGI Ref ID J:54081)
- long bones are at most 10% longer than in wild-type
- kyphosis (MGI Ref ID J:54081)
- growth/size phenotype
- enlarged chest (MGI Ref ID J:54081)
- increase in dorsal-ventral diameter of the chest because of overgrowth of the ribs
- immune system phenotype
- vasculitis (MGI Ref ID J:54081)
- 9 of 20 exhibit medial aorta vasculitis
- limbs/digits/tail phenotype
- increased length of long bones (MGI Ref ID J:54081)
- long bones are at most 10% longer than in wild-type
- muscle phenotype
- herniated diaphragm (MGI Ref ID J:54081)
- half of mice with severe kyphosis exhibit diaphragmatic hernia with thoracic migration of abdominal contents and respiratory distress
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Cardiovascular Research
Heart Abnormalities (aortic aneurysms)
Internal/Organ Research
Heart Abnormalities (aortic aneurysms)
Mouse/Human Gene Homologs
Marfan syndrome
Research Tools
Cardiovascular Research
Internal/Organ Research
| Allele Symbol | Fbn1tm2Rmz | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, Francesco Ramirez | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | mgR; | ||
| Mutation Made By | Francesco Ramirez, UMDNJ-Robert Wood Johnson Med Sch | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Gene Symbol and Name | Fbn1, fibrillin 1 | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | AI536462; FBN; Fib-1; MASS; MFS1; OCTD; SGS; Tsk; WMS; expressed sequence AI536462; tight skin; | ||
| Molecular Note | An unequal crossover event resulted in the insertion of a neomycin selection cassette into intron 18 with no loss of coding sequences. RT-PCR analysis confirmed that correctly spliced transcripts are produced from this allele. Northern blot analysis onmRNA derived from skin samples of homozygous mice demonstrated that transcript expression was reduced approximately five-fold. Immunoprecipitation experiments on fibroblasts isolated from homozygous mice confirmed that a protein was expressed from this allele at reduced levels compared to wild-type. [MGI Ref ID J:54081] | ||
Genotyping Protocols
Fbn1tm2Rmz, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Pereira L; Lee SY; Gayraud B; Andrikopoulos K; Shapiro SD; Bunton T; Biery NJ; Dietz HC; Sakai LY; Ramirez F. 1999. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc Natl Acad Sci U S A 96(7):3819-23. [PubMed: 10097121] [MGI Ref ID J:54081]
Fbn1tm2Rmz relatedBunton TE; Biery NJ; Myers L; Gayraud B; Ramirez F; Dietz HC. 2001. Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ Res 88(1):37-43. [PubMed: 11139471] [MGI Ref ID J:111116]
Marque V; Kieffer P; Gayraud B; Lartaud-Idjouadiene I; Ramirez F; Atkinson J. 2001. Aortic wall mechanics and composition in a transgenic mouse model of Marfan syndrome. Arterioscler Thromb Vasc Biol 21(7):1184-9. [PubMed: 11451749] [MGI Ref ID J:128576]
Zacchigna L; Vecchione C; Notte A; Cordenonsi M; Dupont S; Maretto S; Cifelli G; Ferrari A; Maffei A; Fabbro C; Braghetta P; Marino G; Selvetella G; Aretini A; Colonnese C; Bettarini U; Russo G; Soligo S; Adorno M; Bonaldo P; Volpin D; Piccolo S; Lembo G; Bressan GM. 2006. Emilin1 links TGF-beta maturation to blood pressure homeostasis. Cell 124(5):929-42. [PubMed: 16530041] [MGI Ref ID J:115889]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice are bred. Homozygous mice are subfertile and die between 2-6 months of age. Mating System +/+ sibling x Heterozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Fbn1tm2Rmz *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Heterozygous for Fbn1tm2Rmz x Wild-type for Fbn1tm2Rmz $288.65 Wild-type for Fbn1tm2Rmz x Heterozygous for Fbn1tm2Rmz
| Supply Notes |
|
|---|
| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Fbn1tm2Rmz *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Heterozygous for Fbn1tm2Rmz x Wild-type for Fbn1tm2Rmz $375.30 Wild-type for Fbn1tm2Rmz x Heterozygous for Fbn1tm2Rmz
| Supply Notes |
|
|---|
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.
Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.