Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System +/+ sibling x Heterozygote         (Female x Male) Species laboratory mouse   Donating Investigator Anthony Wynshaw-Boris,   UCSD

Description
Half of homozygotes exhibit a perinatal lethal phenotype. Surviving homozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Some newborn homozygotes fail to survive and exhibit breathing difficulties, cyanosis and reduced mobility. No gene product (protein) is detected by Western blot analysis of brain lystates. Some nonviable homozygotes display cardiac abnormalities. Most homozygotes (90%) have mild abnormalities of the ribs and vertebrae. 2 to 3% of the homozygous embryos display thoracic spina bifida and exencephaly. This mutant mouse strain may be useful in studies of bone and cardiac development, neural tube closure and spina bifida.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt part of exon 2 and exons 3 through 6. The construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice for more than 50 generations. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Transposition of the Great Arteries, Dextro-Looped 1; DTGA1 - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Dvl2^tm1Awb/Dvl2^tm1Awb

        either: 129S6/SvEvTac-Dvl2^tm1Awb or (involves: 129S6/SvEvTac * NIH Swiss)

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:79834)
  • incomplete penetrance; more than 50% die after E18.5
• cardiovascular system phenotype
• abnormal ventricular septum morphology (MGI Ref ID J:79834)
  • frequently observed in conjuction with double outlet right ventricle
• double outlet right ventricle (MGI Ref ID J:79834)
  • most common defect observed by mice with cardiovascular abnormalities
  • frequently observed in conjuction with ventricular septal defects
• persistent truncus arteriosis (MGI Ref ID J:79834)
  • exhibited by several embryos
• transposition of great vessels (MGI Ref ID J:79834)
  • observed in a single embryo
• embryogenesis phenotype
• abnormal somite development (MGI Ref ID J:79834)
  • mild abnormalities in somite segmentation
• homeostasis/metabolism phenotype
• cyanosis (MGI Ref ID J:79834)
  • surviving mice were predominantly female
• limbs/digits/tail phenotype
• kinked tail (MGI Ref ID J:79834)
  • exhibited by 25% of surviving mice
• vestigial tail (MGI Ref ID J:79834)
  • exhibited by some surviving mice
• skeleton phenotype
• abnormal rib morphology (MGI Ref ID J:79834)
  • 90% displayed minor abnormalities
  • normal rib number
• rib bifurcation (MGI Ref ID J:79834)
• rib fusion (MGI Ref ID J:79834)
• abnormal vertebrae morphology (MGI Ref ID J:79834)
  • 90% displayed minor abnormalities
  • defects localized dorsally in vertebral ribs and vertebral bodies
• abnormal thoracic vertebrae morphology (MGI Ref ID J:79834)
  • disorganized thoracic vertebrae
• abnormal xiphoid process (MGI Ref ID J:79834)
  • observed in one neonate
  • affecting the sixth sternebra
• scoliosis (MGI Ref ID J:79834)
  • exhibited by surviving mutant mice
• nervous system phenotype
• exencephaly (MGI Ref ID J:79834)
  • exhibited at E9.5 by 2-3% of mutant mice
• open neural tube (MGI Ref ID J:79834)
  • exhibited at E9.5 by 2-3% of mutant mice
• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:100861)
  • normal stereocilia orientation at E18.5

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects (heart)
Neural Tube Defects
Perinatal Lethality (Homozygous)
Skeletal Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Dvl2tm1Awb
Allele Name		targeted mutation 1, Anthony Wynshaw-Boris
Allele Type		Targeted (knock-out)
Common Name(s)		Dvl2-/-;
Mutation Made By		Anthony Wynshaw-Boris,   UCSD
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Dvl2, dishevelled 2, dsh homolog (Drosophila)
Chromosome		11
Molecular Note		A neomycin selection cassette inserted by homologous recombination replaced a portion of exon 2 and all of exons 3 through 6. Western blot analysis of homozygous mutant brain lysates indicated an absence of protein. [MGI Ref ID J:79834]

Genotyping

Genotyping Information

Genotyping Protocols

Dvl2^tm1Awb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Hamblet NS; Lijam N; Ruiz-Lozano P; Wang J; Yang Y; Luo Z; Mei L; Chien KR; Sussman DJ; Wynshaw-Boris A. 2002. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development 129(24):5827-38. [PubMed: 12421720]  [MGI Ref ID J:79834]

Additional References

Dvl2^tm1Awb related

Gruber PJ; Epstein JA. 2004. Development gone awry: congenital heart disease. Circ Res 94(3):273-83. [PubMed: 14976138]  [MGI Ref ID J:96661]

Kioussi C; Briata P; Baek SH; Rose DW; Hamblet NS; Herman T; Ohgi KA; Lin C; Gleiberman A; Wang J; Brault V; Ruiz-Lozano P; Nguyen HD; Kemler R; Glass CK; Wynshaw-Boris A; Rosenfeld MG. 2002. Identification of a Wnt/Dvl/beta-Catenin --> Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development. Cell 111(5):673-85. [PubMed: 12464179]  [MGI Ref ID J:80691]

Wang J; Hamblet NS; Mark S; Dickinson ME; Brinkman BC; Segil N; Fraser SE; Chen P; Wallingford JB; Wynshaw-Boris A. 2006. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development 133(9):1767-78. [PubMed: 16571627]  [MGI Ref ID J:108512]

Wang J; Mark S; Zhang X; Qian D; Yoo SJ; Radde-Gallwitz K; Zhang Y; Lin X; Collazo A; Wynshaw-Boris A; Chen P. 2005. Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway. Nat Genet 37(9):980-5. [PubMed: 16116426]  [MGI Ref ID J:100861]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes although half of the homozygotes have a perinatal lethal phenotype.
Mating System	+/+ sibling x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply	Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.
Important Note

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
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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fax:	207-288-6655

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