Overview

The Axin^Tg1 transgenic insertional allele has the ~600 kb human epsilon-globin gene inserted between exon 1 and exon 3 (deleting exon 2) of the Axin1 locus. The transgene directs expression of truncated Axin1 mRNA product (still containing exons 3-10) that results in a recessive loss-of-function allele.

Donating Investigator

Frank Costantini, Columbia University Medical Center

Genetic overview

Genetic Background	Generation

Axin1^Fu-Tg1

Allele Type
Transgenic

View Genetics

Research Applications

Developmental Biology Research
Cardiovascular Research
Internal/Organ Research
Cell Biology Research
Apoptosis Research
Research Tools
Neurobiology Research

View All Research Applications

Details

Detailed Description

The Axin^Tg1 transgenic insertional allele (previously called Fu^Tg1 or Hε46) has a tandem array of the human epsilon-globin gene (~600 kb in total) inserted between exon 1 and exon 3 (deleting exon 2) of the Axin1 locus. The transgene directs expression of a truncated Axin1 mRNA product (still containing exons 3-10) that results in a recessive loss-of-function allele. Homozygous Axin^Tg1 mice die between embryonic day (E)8-E10 with abnormalities in developmental patterning (duplication of embryonic axis and parts of the embryo) and nervous system development (truncated headfolds, severely underdeveloped/absent forebrain, and kinked neural tube). Some incidence of cardia bifida and enlarged pericardium are reported in severely affected homozygotes. These Axin^Tg1 mutant mice may be useful for studying developmental patterning, axis duplication, forebrain development, negative regulation of canonical Wnt signaling pathway, β-catenin/cadherin function, and apoptosis.

Development

An 8.1 kb transgene harboring a tandem array of the human epsilon-globin gene (~600 kb in total) was microinjected into (CBA/J x C57BL/6J)F2 zygotes, and founder mice were bred to (CBA/J x C57BL/6J)F1 mice. Transgenic founder line 46 (Hε46) was established on a CBA/J;C57BL/6J hybrid background and found to have the transgene inserted between exon 1 and exon 3 of the Axin1 locus; also resulting in deletion of exon 2 and parts of the two flanking introns. Mice heterozygous for this Axin^Tg1 transgenic insertional allele (previously called Fu^Tg1 or Hε46), were backcrossed to C57BL/6J inbred mice for approximately 20 generations by the laboratory of Dr. Frank Costantini (Columbia University Medical Center). Heterozygous embryos were then cryopreserved. Aliquots of these frozen embryos were sent to Mutant Mouse Regional Resource Center node at The Jackson Laboratory (Mmjax) and used to establish a live mutant colony.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Perry WL 3rd; Vasicek TJ; Lee JJ; Rossi JM; Zeng L; Zhang T; Tilghman SM; Costantini F. 1995. Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. Genetics 141(1):321-32PubMed: 8536979 MGI: J:28303
Zeng L; Fagotto F; Zhang T; Hsu W; Vasicek TJ; Perry WL 3rd ; Lee JJ ; Tilghman SM ; Gumbiner BM ; Costantini F. 1997. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 90(1):181-92PubMed: 9230313 MGI: J:41619

View All References

Genetics

Axin1^Fu-Tg1

Allele Symbol: Axin1^Fu-Tg1

Allele Name	fused transgenic 1
Allele Type	Transgenic
Allele Synonym(s)	Axin^Tg1; H epsilon 46
Gene Symbol and Name	Axin1, axin 1
Gene Synonym(s)
Strain of Origin	(CBA/J x C57BL/6J)F2
Chromosome	17
Molecular Note	In this mutation, an ~600 kb transgene is inserted between exons 1 and 3, and exon 2 and 20 kb from the two flanking introns are deleted. This disruption results in the absence of the major wild-type 3.9 kb mRNA in homozygotes.
Mutations Made By	Frank Costantini, Columbia University Medical Center

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Growth Defects
  - Growth Defects (homozygous)
- Internal/Organ Defects
  - brain
  - multiple
  - heart
- Neurodevelopmental Defects
- Embryonic Lethality (Homozygous)
Cardiovascular Research
- Heart Abnormalities
Internal/Organ Research
- Heart Abnormalities
Cell Biology Research
- Signal Transduction
Apoptosis Research
- Endogenous Regulators
Research Tools
- Apoptosis Research
- Developmental Biology Research
Neurobiology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Axin1^Fu-Tg1/Axin1^Fu-Tg1
involves: C57BL/6J * CBA/J

cardiovascular system phenotype

cardia bifida
- seen in severely affected mutants

enlarged pericardium
- heart appears normal in most cases, however occasionally the pericardium is abnormally expanded

growth/size/body region phenotype

decreased embryo size

embryonic growth retardation
- developmental delay at E9.5
- most mutants at E8.5 appear retarded in development, resembling E8 embryos

shortened head
- truncated head at E9.5

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- lethality around E9 to E10

nervous system phenotype

absent forebrain
- forebrain is absent or severely underdeveloped by E9.5

forebrain hypoplasia
- forebrain is absent or severely underdeveloped by E9.5

incomplete rostral neuropore closure
- by E9.5, the head folds usually failed to close
- open head folds

kinked neural tube

craniofacial phenotype

shortened head
- truncated head at E9.5

embryo phenotype

abnormal allantois morphology
- some exhibit two allantoises connected to the placenta

abnormal amniotic cavity morphology
- abnormal accumulation of cellular debris in the amniotic cavity

abnormal axial mesoderm morphology
- E8.5 embryos exhibit duplication of anterior axial mesoderm

abnormal embryonic tissue morphology
- some embryos have extra structures near the head folds, often protruding through the yolk sac and in other cases, the head folds appear to protrude through the yolk sac
- the posterior end of the primary embryo protrudes through the visceral yolk sac in to the yolk cavity

decreased embryo size

embryonic growth retardation
- developmental delay at E9.5
- most mutants at E8.5 appear retarded in development, resembling E8 embryos

incomplete rostral neuropore closure
- by E9.5, the head folds usually failed to close
- open head folds

kinked neural tube

rostral-caudal axis duplication
- exhibit duplication of the embryonic axis and parts of the embryo

References

Perry WL 3rd; Vasicek TJ; Lee JJ; Rossi JM; Zeng L; Zhang T; Tilghman SM; Costantini F. 1995. Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. Genetics 141(1):321-32PubMed: 8536979 MGI: J:28303
Zeng L; Fagotto F; Zhang T; Hsu W; Vasicek TJ; Perry WL 3rd ; Lee JJ ; Tilghman SM ; Gumbiner BM ; Costantini F. 1997. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 90(1):181-92PubMed: 9230313 MGI: J:41619

Additional - Axin1^Fu-Tg1 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Axin1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, hemizygous mice may be bred to wildtype siblings or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice die in utero.
- Additional Breeding and Husbandry Support
Citation
When using the B6.Cg-Axin1^Fu-Tg1/CosMmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32035 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Axin1Fu-Tg1

Allele Symbol: Axin1Fu-Tg1

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Axin1Fu-Tg1/Axin1Fu-Tg1involves: C57BL/6J * CBA/J

cardiovascular system phenotype

growth/size/body region phenotype

mortality/aging

nervous system phenotype

craniofacial phenotype

embryo phenotype

References

Additional - Axin1Fu-Tg1 related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Axin1^Fu-Tg1

Allele Symbol: Axin1^Fu-Tg1

Genotype: Axin1^Fu-Tg1/Axin1^Fu-Tg1
involves: C57BL/6J * CBA/J

Additional - Axin1^Fu-Tg1 related