Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   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 wild-type siblings.

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.

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 and C57BL/6 then backcrossed to DBA/2J for at least 10 generations.

Related Strains

Strains carrying   Fn1^tm1Hyn allele

008444	129S4.129S2(B6)-Fn1tm1Hyn/J
008445	B6.129S-Fn1tm1Hyn/2J
002270	B6.129S-Fn1tm1Hyn/J

View Strains carrying   Fn1^tm1Hyn     (3 strains)

Strains carrying other alleles of Fn1

008444	129S4.129S2(B6)-Fn1tm1Hyn/J
008445	B6.129S-Fn1tm1Hyn/2J
002270	B6.129S-Fn1tm1Hyn/J
008595	B6;129P2-Fn1tm4Hyn/J

View Strains carrying other alleles of Fn1     (4 strains)

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

View Research Applications

Research Applications

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

Cardiovascular Research
Heart Abnormalities
Vascular Defects

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

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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

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

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

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred. Homozygotes are embryonic lethal.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Payment Terms and Conditions

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

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

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.