Description

Strain Information

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 Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Fbn1

000305

B6.Cg-Fbn1Tsk +/+ Pldnpa/J

View Strains carrying other alleles of Fbn1     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Fbn1^tm2Rmz/Fbn1^tm2Rmz

        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
• hemopericardium (MGI Ref ID J:54081)
• hemothorax (MGI Ref ID J:54081)
• 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

Genes & Alleles

Gene & Allele Information

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

Genotyping Information

Genotyping Protocols

Fbn1^tm2Rmz, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

Fbn1^tm2Rmz related

Bunton 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]

Health & husbandry

Health & Colony Maintenance Information

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

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

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	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.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

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Ordering and Purchasing Information

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Contact Information
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Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

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