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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Richard Hynes,   Massachusetts Institute of Technology

Description
Alternatively spliced exons EIIIA and EIIIB of the fibronectin 1 (Fn1) gene are deleted in these double targeted mutant mice. Embryonic lethality with incomplete penetrance is observed in homozygotes by embryonic day 10.5. Homozygous embryos display multiple embryonic cardiovascular defects, including vascular hemorrhage, failure of remodeling embryonic and yolk sac vasculature, defective placental angiogenesis and heart defects. Synthesis and cell surface deposition of fibronectin 1 are not affected. This strain may be helpful in studies of cardiovascular development.

Development
ES cells from homozygous Fn1^tm1Ksek male mouse (mixed 129P2/OlaHsd and C57BL/6J background) in which exon EDB (EIIIB) was deleted and replaced with a singe loxp site was isolated and targeted with the same construct used in Fn1^tm1Bwg. Following homologous recombination and transient cre-mediated recombination, a single loxp site was left in place of the exon encoding the EIIIA domain. This compound mutant line has been maintained on a mixed C57BL/6 and 129 background by the donating laboratory.

Related Strains

Strains carrying other alleles of Fn1

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

Fn1^tm4Hyn/Fn1^tm4Hyn

        involves: 129P2/OlaHsd * C57BL/6J

• mortality/aging
• partial embryonic lethality during organogenesis
  • embryonic lethal with about 80% penetrance, 50% of E9.5 and 80% of E10.5 mutant embryos showed severe cardiovascular defects and were absorbed by E11.0 in mixed background compared to congenic strain of 129 or B6   (MGI Ref ID J:126737)
• cardiovascular system phenotype
• abnormal atrioventricular cushion morphology
  • in some abnormal E10.5 embryos   (MGI Ref ID J:126737)
• abnormal outflow tract development
  • thinned outflow tract in 30% of all defective embryos by E10.5   (MGI Ref ID J:126737)
• abnormal placenta vasculature
  • placental vascularization following the invasion with embryonic vessels was much less extensive in about 50% of mutant embryos   (MGI Ref ID J:126737)
• abnormal vascular development
  • in severely affected mutant E9.5 embryos, dysmorphic large vessels in the head and small vessels in the head and body appeared syncytial with endothelial cells forming sheets instead of tubes   (MGI Ref ID J:126737)
  • in less severely affected, abnormally patterned, blunt-ended and constricted head veins   (MGI Ref ID J:126737)
• • abnormal vitelline vascular remodeling
    • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
  • absent vitelline blood vessels
    • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
  • disorganized yolk sac vascular plexus
    • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
• abnormal vascular smooth muscle morphology
  • a decrease in the number of vascular smooth muscle cells in E10.5 embryos   (MGI Ref ID J:126737)
• distended pericardium
  • in 50% of all defective embryos by E10.5   (MGI Ref ID J:126737)
• hemorrhage
  • within the 83% of all defective embryos by E9.5 and 100% by E10.5   (MGI Ref ID J:126737)
  • focal head hemorrhage in a small number of morphologically normal E10.5 embryos   (MGI Ref ID J:126737)
• hematopoietic system phenotype
• anemia
  • in defective embryos due to leakage of blood by E9.5   (MGI Ref ID J:126737)
• nervous system phenotype
• kinked neural tube
  • shortened posterior, kinked neural tube in 5% of all defective embryos by E9.5   (MGI Ref ID J:126737)
• embryogenesis phenotype
• abnormal placenta vasculature
  • placental vascularization following the invasion with embryonic vessels was much less extensive in about 50% of mutant embryos   (MGI Ref ID J:126737)
• abnormal visceral yolk sac morphology
  • separation of endodermal and mesodermal layer resulting in blistered appearance of the yolk sac in 30% of all defective embryos by E9.5   (MGI Ref ID J:126737)
• • abnormal vitelline vascular remodeling
    • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
  • disorganized yolk sac vascular plexus
    • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
• absent vitelline blood vessels
  • in some embryos with blistered yolk sac   (MGI Ref ID J:126737)
• kinked neural tube
  • shortened posterior, kinked neural tube in 5% of all defective embryos by E9.5   (MGI Ref ID J:126737)
• muscle phenotype
• abnormal vascular smooth muscle morphology
  • a decrease in the number of vascular smooth muscle cells in E10.5 embryos   (MGI Ref ID J:126737)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Fn1^tm4Hyn/Fn1^tm4Hyn

        129S4.129P2-Fn1^tm4Hyn

• mortality/aging
• complete prenatal lethality
  • embryonic lethal with 100% penetrance in 129S4 congenic background compared to B6 congenic or mixed B6-129 background, timing of death was not stated   (MGI Ref ID J:126737)

Fn1^tm4Hyn/Fn1^tm4Hyn

        B6.129P2-Fn1^tm4Hyn

• mortality/aging
• partial prenatal lethality
  • embryonic lethal with about 50% penetrance in B6 congenic background compared to 129 congenic or mixed B6-129 background, timing of death was not stated   (MGI Ref ID J:126737)

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
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      heart
      heart: vasculature
      vasculature

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fn1tm4Hyn
Allele Name		targeted mutation 4, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		EIIIA/EIIIB-double-null; EIIIA-EIIIB-;
Mutation Made By		Richard Hynes,   Massachusetts Institute of Technology
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		Other (see notes)
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;
General Note		ES cells were derived from male homozygous Fn1tm1Ksek mouse of a mixed 129P2/OlaHsd and C57BL/6J background strain.
Molecular Note		ES cells from homozygous Fn1tm1Ksek male mouse in which exon EDB (EIIIB) was deleted and replaced with a singe loxp site was isolated and targeted with the same construct used in Fn1tm1Bwg. Following homologous recombination and transient cre-mediated recombination, a single loxp site was left in place of the exon encoding the EIIIA domain. Northern and Western blot confirmed the absence of EIII1 and EIIIB mRNA and protein and that deletion of both of those exons did not compromisethe expression of FN mRNA and protein, nor the deposition of FN into the matrix. [MGI Ref ID J:126737]

Genotyping

Genotyping Information

Genotyping Protocols

Fn1^tm4Hyn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Astrof S; Crowley D; Hynes RO. 2007. Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectin. Dev Biol 311(1):11-24. [PubMed: 17706958]  [MGI Ref ID J:126737]

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 are embryonic lethal (incomplete penetrance).

Purchasing information

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General Supply Notes

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

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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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