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 Dr. Anthony Wynshaw-Boris,   UCSF

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of MEF (mouse embryonic fibroblasts) derived from homozygotes. Homozygotes exhibit diminished social interaction behavior, do not barber or trim whiskers of cagemates, show subordinance in social dominance tests, do not sleep huddled together and do not build nests. Although mutants have an attenuated prepulse inhibition of acoustic and tactile startle (sensorimotor gating of the startle reflex), they do not exhibit any deficits in locomotor or cognitive function. This mutant mouse strain may be useful in studies of social behavior, sensorimotor gating, and possibly psychiatric disorders.

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 and 4, encoding amino acids 131-225. 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 mice, and then backcrossed to 129S6/SvEvTac 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
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying   Dvl1^tm1Awb allele

007969

B6.129S6-Dvl1tm1Awb/J

View Strains carrying   Dvl1^tm1Awb     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Dvl1^tm1Awb/Dvl1^tm1Awb

        involves: 129S6/SvEvTac

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • homozygotes are viable, fertile and display no motor deficits or differences in pain sensitivity relative to wild-type mice   (MGI Ref ID J:42758)
  • no significant differences in spatial learning and memory are observed   (MGI Ref ID J:42758)
• • abnormal social/conspecific interaction
    • when housed separately as uniform genotypes, homozygotes display only 2 episodes of social behaviors whereas wild-type mice display 44 episodes including social grooming, mounting, tail pulling and sniffing; however, the frequency of self-grooming is not significantly different between wild-type and mutant mice (41 vs 36 episodes, respectively)   (MGI Ref ID J:42758)
    • when paired against each other in the social dominance tube test, homozygotes display a significantly lower percentage of wins than sex-matched wild-type mice (~30% vs 73%, respectively)   (MGI Ref ID J:42758)
  • • abnormal huddling behavior
      • homozygotes sleep in scattered random patterns, unlike wild-type mice which generally sleep huddled together   (MGI Ref ID J:42758)
      • over a period of time, homozygotes tend to loosely huddle in various quandrants of the cage, whereas wild-type mice are more often observed huddled in the same quadrant   (MGI Ref ID J:42758)
    • abnormal nest building behavior
      • homozygotes build significantly shallower nests from nest building material relative to wild-type controls   (MGI Ref ID J:42758)
      • homozygotes tend to sleep on top of intact nestlet material whereas wild-type mice sleep in well-formed, fluffy nests   (MGI Ref ID J:42758)
      • however, abnormal nesting behavior is not due to differences in rectal temperatures   (MGI Ref ID J:42758)
  • abnormal whisker trimming behavior
    • homozygotes do not trim/barber their cagemates' whiskers or facial hair, unlike the majority of separately housed wild-type littermates which lack whiskers and have trimmed facial hair   (MGI Ref ID J:42758)
    • when housed separately as uniform genotypes, all post-weaning homozygotes between 2 and 9 months of age display full sets of whiskers and facial hair, relative to only 25%-50% of age-matched wild-type controls   (MGI Ref ID J:42758)
    • when housed with wild-type mice, homozygotes lose all whiskers and facial hair in 5 of 11 cages after mixed housing and regrow their whiskers within 2 weeks after returning to their home cage; in contrast, whiskerless wild-type mice consistently regrow full sets of whiskers and facial hair within 2-4 weeks after mixed genotype housing and have their whiskers trimmed within 2 weeks of return to their home cage   (MGI Ref ID J:42758)
  • decreased startle reflex
    • homozygotes display attenuated responses to acoustic startle stimuli relative to wild-type mice   (MGI Ref ID J:42758)
    • in contrast, tactile startle reponses remain unaffected   (MGI Ref ID J:42758)
• nervous system phenotype
• *normal* nervous system phenotype
  • homozygotes display normal brain histology and synaptic plasticity relative to wild-type mice   (MGI Ref ID J:42758)
• • decreased prepulse inhibition
    • homozygotes display significantly lower levels of acoustic pre-pulse inhibition of both acoustic and tactile startle responses relative to wild-type mice   (MGI Ref ID J:42758)
  • reduced sensorimotor gating
    • homozygotes display significantly lower levels of acoustic pre-pulse inhibition of both acoustic and tactile startle responses relative to wild-type mice   (MGI Ref ID J:42758)
• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype
  • homozygotes exhibit normal stereocilia orientation at E18.5   (MGI Ref ID J:100861)

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects

Sensorineural Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dvl1tm1Awb
Allele Name		targeted mutation 1, Anthony Wynshaw-Boris
Allele Type		Targeted (knock-out)
Common Name(s)		Dvl1-; Dvl1del131-225;
Mutation Made By		Dr. Anthony Wynshaw-Boris,   UCSF
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TC1/TC-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Dvl1, dishevelled, dsh homolog 1 (Drosophila)
Chromosome		4
Gene Common Name(s)		DVL; DVL1L1; dvl-1;
Molecular Note		A neomycin selection cassette replaced a genomic fragment containing part of exon 2 and exons 3 and 4, which encode amino acids 131-225. Western blot analysis on embryonic fibroblasts derived from homozygous mice confirmed that no detectable protein wasproduced from this allele. [MGI Ref ID J:42758]

Genotyping

Genotyping Information

Genotyping Protocols

Dvl1^tm1Awb, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lijam N; Paylor R; McDonald MP; Crawley JN; Deng CX; Herrup K ; Stevens KE ; Maccaferri G ; McBain CJ ; Sussman DJ ; Wynshaw-Boris A. 1997. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell 90(5):895-905. [PubMed: 9298901]  [MGI Ref ID J:42758]

Additional References

Dvl1^tm1Awb related

Ahmad-Annuar A; Ciani L; Simeonidis I; Herreros J; Fredj NB; Rosso SB; Hall A; Brickley S; Salinas PC. 2006. Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release. J Cell Biol 174(1):127-39. [PubMed: 16818724]  [MGI Ref ID J:111190]

Ciani L; Boyle KA; Dickins E; Sahores M; Anane D; Lopes DM; Gibb AJ; Salinas PC. 2011. Wnt7a signaling promotes dendritic spine growth and synaptic strength through Ca2+/Calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A 108(26):10732-7. [PubMed: 21670302]  [MGI Ref ID J:173542]

Etheridge SL; Ray S; Li S; Hamblet NS; Lijam N; Tsang M; Greer J; Kardos N; Wang J; Sussman DJ; Chen P; Wynshaw-Boris A. 2008. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development. PLoS Genet 4(11):e1000259. [PubMed: 19008950]  [MGI Ref ID J:142392]

Glasco DM; Sittaramane V; Bryant W; Fritzsch B; Sawant A; Paudyal A; Stewart M; Andre P; Cadete Vilhais-Neto G; Yang Y; Song MR; Murdoch JN; Chandrasekhar A. 2012. The mouse Wnt/PCP protein Vangl2 is necessary for migration of facial branchiomotor neurons, and functions independently of Dishevelled. Dev Biol 369(2):211-22. [PubMed: 22771245]  [MGI Ref ID J:187622]

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]

Henriquez JP; Webb A; Bence M; Bildsoe H; Sahores M; Hughes SM; Salinas PC. 2008. Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin. Proc Natl Acad Sci U S A 105(48):18812-7. [PubMed: 19020093]  [MGI Ref ID J:142354]

Long JM; LaPorte P; Paylor R; Wynshaw-Boris A. 2004. Expanded characterization of the social interaction abnormalities in mice lacking Dvl1. Genes Brain Behav 3(1):51-62. [PubMed: 14960015]  [MGI Ref ID J:101889]

Purro SA; Ciani L; Hoyos-Flight M; Stamatakou E; Siomou E; Salinas PC. 2008. Wnt regulates axon behavior through changes in microtubule growth directionality: a new role for adenomatous polyposis coli. J Neurosci 28(34):8644-54. [PubMed: 18716223]  [MGI Ref ID J:138829]

Rosso SB; Sussman D; Wynshaw-Boris A; Salinas PC. 2005. Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development. Nat Neurosci 8(1):34-42. [PubMed: 15608632]  [MGI Ref ID J:95820]

Sinha T; Wang B; Evans S; Wynshaw-Boris A; Wang J. 2012. Disheveled mediated planar cell polarity signaling is required in the second heart field lineage for outflow tract morphogenesis. Dev Biol 370(1):135-44. [PubMed: 22841628]  [MGI Ref ID J:188039]

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]

van de Schans VA; van den Borne SW; Strzelecka AE; Janssen BJ; van der Velden JL; Langen RC; Wynshaw-Boris A; Smits JF; Blankesteijn WM. 2007. Interruption of Wnt signaling attenuates the onset of pressure overload-induced cardiac hypertrophy. Hypertension 49(3):473-80. [PubMed: 17210832]  [MGI Ref ID J:149056]

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, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	None Available
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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