Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S2/SvPas via D3 ES cell line Generation N10p+N1   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
Mice homozygous for the Fn1^tm1Hyn targeted mutation die during early embryonic development. Blastocyst development and implantation of homozygotes is normal. Gastrulation is initiated and appears normal, including extensive mesodermal movement. From embryonic day 8 onwards homozygous mutant embryos deteriorate through the 10th and 11th days of gestation. Homozygous mutant embryos have a shortened anterior-posterior axes, fail to develop a notochord or somites, and have abnormal development of the heart, blood vessels, and yolk sac indicating a general deficiency in mesodermally derived tissues. Heterozygous mice are viable for at least 2 years and appear healthy and approximately the same size as wild-type littermates. Plasma levels of fibronectin in heterozygotes are 50% lower than normal wildtype siblings.

Development
A PGK-neomycin resistance cassette replaced 0.8 kb of the gene including the translation initiation site and part of the signaling sequence. This mutation was created in 129S2/SvPas-derived D3 embryonic stem (ES) cells. The mice were bred to 129S4/SvJae then backcrossed to C57BL/6 for at least 11 generations.

Control Information

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

Related Strains

Strains carrying   Fn1^tm1Hyn allele

008444	129S4.129S2(B6)-Fn1tm1Hyn/J
008445	B6.129S-Fn1tm1Hyn/2J
008443	D2.129S2(Cg)-Fn1tm1Hyn/J

View Strains carrying   Fn1^tm1Hyn     (3 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

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.

Fn1^tm1Hyn/Fn1^tm1Hyn

        involves: 129S2/SvPas * C57BL/6J

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:16247)
  • homozygotes develop severe embryonic abnormalities from E8.0 onwards and undergo degeneration during E10 and E11
• cardiovascular system phenotype
• abnormal aorta morphology (MGI Ref ID J:16247)
• abnormal cardiac muscle morphology (MGI Ref ID J:16247)
  • at E8.5, homozygotes display a thickened myocardium; cardiac jelly is deficient
• abnormal dorsal aorta morphology (MGI Ref ID J:16247)
  • at E8.5, severely affected embryos show absence of dorsal aortae while less severely affected embryos exhibit distended dorsal aortae containing only a few blood cells
• abnormal endocardium morphology (MGI Ref ID J:16247)
  • at E8.5, the mutant endocardium is either indistinguishable from the thickened myocardium or absent
• abnormal heart development (MGI Ref ID J:16247)
  • at E8.5, 13 of 20 mutant embryos have a visible primitive heart whereas the remaining seven do not
  • in severely affected embryos, heart primordia fail to fuse and are positioned laterally
• abnormal vasculogenesis (MGI Ref ID J:16247)
  • at E8.5, homozygotes display defective vasculogenesis in the yolk sac
  • mutant embryonic vessels appear variable and deformed while extraembryonic vasculature is also defective
• embryogenesis phenotype
• abnormal developmental patterning (MGI Ref ID J:16247)
• abnormal ectoderm development (MGI Ref ID J:16247)
  • at E8.0, homozygotes display multiple bends and distortions in the neural ectoderm
• abnormal mesoderm development (MGI Ref ID J:16247)
  • at E8.0, homozygotes exhibit a deficit in the trunk and headfold mesoderm
  • by E8.5, mutant headfolds appear small and misshapen, with a deficit in underlying mesoderm and many pyknotic cells; lateral mesoderm flanking the neural tube is reduced
• abnormal rostral-caudal axis patterning (MGI Ref ID J:16247)
  • at E8.0, homozygotes display a shortened anterior-posterior axis
• failure of initiation of embryo turning (MGI Ref ID J:16247)
  • at E8.5, none of the mutant embryos have initiated turning
• abnormal embryonic tissue morphology (MGI Ref ID J:16247)
• absent notochord (MGI Ref ID J:16247)
  • at E8.5, homozygotes lack an organized notochord; instead, the endodermal lining of the future midgut is juxtaposed to the neural tube
• absent somites (MGI Ref ID J:16247)
  • at E8.5, mutant embryos lack somites whereas wild-type embryos contain 8 to 12 pairs of somites; however, condensations of cells suggestive of incipient somites are detected in 3 of 20 mutants
• abnormal extraembryonic tissue morphology (MGI Ref ID J:16247)
• abnormal amnion morphology (MGI Ref ID J:16247)
  • at E7.5, mutant embryos possess three germ layers and normal extraembryonic membranes except for a concave amnion
  • at E8.0, the mutant amnion is undersized and closely apposed to the embryo, displaying a pressure deficit in the amniotic cavity
• abnormal chorioallantoic fusion (MGI Ref ID J:16247)
  • at E8.5, the allantois has yet not fused with the chorion
• abnormal yolk sac morphology (MGI Ref ID J:16247)
  • at E8.5, the mesodermal and endodermal layers of the mutant yolk sac appear to split apart
• absent blood islands (MGI Ref ID J:16247)
• absent vitelline blood vessels (MGI Ref ID J:16247)
  • at E8.5, blood vessels are detected in the exocoelomic cavity rather than in the yolk sac
• embryonic growth retardation (MGI Ref ID J:16247)
  • starting at E8.0, homozygotes appear developmentally retarded and abnormal
• reduced embryo size (MGI Ref ID J:16247)
  • at E7.5, mutant embryos appear relatively normal, though slightly smaller than wild-type embryos
• nervous system phenotype
• abnormal neural tube morphology/development (MGI Ref ID J:16247)
• kinked neural tube (MGI Ref ID J:16247)
  • at E8.5, homozygotes display a kinked neural tube
• growth/size phenotype
• embryonic growth retardation (MGI Ref ID J:16247)
  • starting at E8.0, homozygotes appear developmentally retarded and abnormal
• reduced embryo size (MGI Ref ID J:16247)
  • at E7.5, mutant embryos appear relatively normal, though slightly smaller than wild-type embryos
• muscle phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:16247)
  • at E8.5, homozygotes display a thickened myocardium; cardiac jelly is deficient

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Fn1^tm1Hyn related

Cardiovascular Research
Heart Abnormalities
Vascular Defects

Developmental Biology Research
Defects in Extracellular Matrix Molecules
Internal/Organ Defects (heart: vasculature)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Fn1tm1Hyn
Allele Name		targeted mutation 1, Richard O Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		FN.null; FNnull; Fn-/-;
Mutation Made By		Richard Hynes,   Massachusetts Institute of Technology
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Fn1, fibronectin 1
Chromosome		1
Gene Common Name(s)		CIG; DKFZp686F10164; DKFZp686H0342; DKFZp686I1370; DKFZp686O13149; ED-B; FIBNEC; FINC; FN; FNZ; Fn-1; GFND; GFND2; LETS; MSF;
Molecular Note		A PGK-neomycin resistance cassette replaced 0.8 kb of the gene including the translation initiation site and part of the signaling sequence. Plasma concentrations of fibronectin in heterozygotes were one-half those of wild-type littermates. The encoded protein was not detectable in immunoprecipitations from cultures of homozygous mutant E7.5 embryos. [MGI Ref ID J:16247]

Genotyping

Genotyping Information

Genotyping Protocols

Fn1^tm1Hyn, STD PCR, vers. 1
Fn1^tm1Hyn, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

George EL; Georges-Labouesse EN; Patel-King RS; Rayburn H; Hynes RO. 1993. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119(4):1079-91. [PubMed: 8306876]  [MGI Ref ID J:16247]

Additional References

George EL; Baldwin HS; Hynes RO. 1997. Fibronectins are essential for heart and blood vessel morphogenesis but are dispensable for initial specification of precursor cells. Blood 90(8):3073-81. [PubMed: 9376588]  [MGI Ref ID J:43434]

Georges-Labouesse EN; George EL; Rayburn H; Hynes RO. 1996. Mesodermal development in mouse embryos mutant for fibronectin. Dev Dyn 207(2):145-56. [PubMed: 8906418]  [MGI Ref ID J:36210]

Fn1^tm1Hyn related

Astrof S; Kirby A; Lindblad-Toh K; Daly M; Hynes RO. 2007. Heart development in fibronectin-null mice is governed by a genetic modifier on chromosome four. Mech Dev 124(7-8):551-8. [PubMed: 17628448]  [MGI Ref ID J:134424]

George EL; Baldwin HS; Hynes RO. 1997. Fibronectins are essential for heart and blood vessel morphogenesis but are dispensable for initial specification of precursor cells. Blood 90(8):3073-81. [PubMed: 9376588]  [MGI Ref ID J:43434]

Georges-Labouesse EN; George EL; Rayburn H; Hynes RO. 1996. Mesodermal development in mouse embryos mutant for fibronectin. Dev Dyn 207(2):145-56. [PubMed: 8906418]  [MGI Ref ID J:36210]

Ilic D; Kovacic B; Johkura K; Schlaepfer DD; Tomasevic N; Han Q; Kim JB; Howerton K; Baumbusch C; Ogiwara N; Streblow DN; Nelson JA; Dazin P; Shino Y; Sasaki K; Damsky CH. 2004. FAK promotes organization of fibronectin matrix and fibrillar adhesions. J Cell Sci 117(Pt 2):177-87. [PubMed: 14657279]  [MGI Ref ID J:87891]

Taverna D; Ullman-Cullere M; Rayburn H; Bronson RT; Hynes RO. 1998. A test of the role of alpha5 integrin/fibronectin interactions in tumorigenesis. Cancer Res 58(4):848-53. [PubMed: 9485045]  [MGI Ref ID J:45769]

Yang JT; Bader BL; Kreidberg JA; Ullman-Cullere M; Trevithick JE; Hynes RO. 1999. Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development. Dev Biol 215(2):264-77. [PubMed: 10545236]  [MGI Ref ID J:58411]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
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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Contact Information
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Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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