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
These mice carry a targeted mutation in the fibronectin 1 gene identical to that found in Stock No. 002270.

This line, backcrossed more than 13 times to C57BL/6J in the donating investigator's colony, has been used in a search for cardiac development modifier genes demonstrating phenotypic differences on C57BL/6J and 129S4/SvJae genetic backgrounds (Astrof, 2007).

In the majority of 129S4 background homozygous targeted mutant embryos, heart progenitors remain at their anterior bilateral positions and fail to fuse at the midline to form a heart tube. However, on the C57BL/6J genetic background, cardiac development progresses further and results in a centrally-positioned looped heart.

Linkage analysis led to the identification of a 1-Mbp interval on mouse Chromosome 4 containing 21 genes, including five that are differentially expressed between C57BL/6J and 129S4/SvJae.

This strain may be helpful in studies of cardiac development.

Development
A PGK-neomycin resistance cassette replaced 0.8 kb of the targeted gene including the translation initiation site and part of the signal 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/6J in the donating investigator's colony for at least 13 generations. The strain was sperm-cryopreserved and will typically be recovered using C57BL/6J females maintained at The Jackson Laboratory.

Related Strains

Strains carrying   Fn1^tm1Hyn allele

008444	129S4.129S2(B6)-Fn1tm1Hyn/J
002270	B6.129S-Fn1tm1Hyn/J
008443	D2.129S2(Cg)-Fn1tm1Hyn/J

View Strains carrying   Fn1^tm1Hyn     (3 strains)

Strains carrying other alleles of Fn1

008444	129S4.129S2(B6)-Fn1tm1Hyn/J
002270	B6.129S-Fn1tm1Hyn/J
008595	B6;129P2-Fn1tm4Hyn/J
008443	D2.129S2(Cg)-Fn1tm1Hyn/J

View Strains carrying other alleles of Fn1     (4 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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

• mortality/aging
• complete 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 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 cardiac jelly morphology
    • at E8.5, cardiac jelly is deficient   (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)
• 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)
• thick myocardium
  • at E8.5, homozygotes display a thickened myocardium   (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   (MGI Ref ID J:16247)
  • • abnormal lateral plate mesoderm morphology
      • by E8.5, 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   (MGI Ref ID J:16247)
  • • abnormal lateral plate mesoderm morphology
      • by E8.5, 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 visceral 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 visceral yolk sac 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)

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
      heart: vasculature

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fn1tm1Hyn
Allele Name		targeted mutation 1, Richard 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; 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 provided by MGI

Selected Reference(s)

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]

Morry MJ; Harding JD. 1986. Modulation of transcriptional activity and stable complex formation by 5'-flanking regions of mouse tRNAHis genes. Mol Cell Biol 6(1):105-15. [PubMed: 3641049]  [MGI Ref ID J:16297]

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

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]

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]

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]

Mittal A; Pulina M; Hou SY; Astrof S. 2010. Fibronectin and integrin alpha 5 play essential roles in the development of the cardiac neural crest. Mech Dev 127(9-12):472-84. [PubMed: 20807571]  [MGI Ref ID J:165711]

Pulina MV; Hou SY; Mittal A; Julich D; Whittaker CA; Holley SA; Hynes RO; Astrof S. 2011. Essential roles of fibronectin in the development of the left-right embryonic body plan. Dev Biol 354(2):208-20. [PubMed: 21466802]  [MGI Ref ID J:173656]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

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

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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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