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 Andrew P McMahon,   University of Southern California

Description
Mice that are homozygous for the targeted mutation are viable, but sterile. A truncated mRNA transcript is detected during embryogenesis. Homozygotes exhibit ventralization of dorsal limb mesoderm tissues. The variable phenotype includes thickening of dorsal limb dermus, loss of dorsal hair on digits and abnormal or missing posterior distal digits. Abnormalities are more severe distally than proximally. Homozygous female mice have functioning ovaries, but are sterile due to abnormal development of the oviduct and uterus. Although homozygous male mice have normal spermatogenesis, Mullerian ducts do not regress resulting in blocked sperm passage. Mutant mice have reduced synapsin I levels and delayed synaptogenesis between cerebellar granule cells and mossy fiber neurons. This mutant mouse strain may be useful in studies related to dorsal-ventral and anterior-posterior patterning and axonal remodeling.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2 of the targeted gene. The construct was electroporated into 129S1/Sv-p⁺ Tyr⁺ Kitl^Sl-J/+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts.

Control Information

	Control
	See control note:	Wildtype mice from the colony or B6129SF2/J (Stock # 101045)can be used as controls.
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Wnt7a

018166	B6;C3Fe-Wnt7apx-2J/GrsrJ
016098	C57BL/6J-Wnt7apx-J/GrsrJ
001253	STOCK MitfMi-wh +/+ Wnt7apx/J

View Strains carrying other alleles of Wnt7a     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Fibular Aplasia or Hypoplasia, Femoral Bowing and Poly-, Syn-, and Oligodactyly   (WNT7A) Ulna and Fibula, Absence of, with Severe Limb Deficiency   (WNT7A)

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.

Wnt7a^tm1Amc/Wnt7a^tm1Amc

        involves: 129S1/Sv

• limbs/digits/tail phenotype
• abnormal limb morphology
  • interactions between signals for the two axes may be required for normal limb development   (MGI Ref ID J:23922)
  • abnormal limb development; dorsal to ventral transformation of cell fate in distal limbs including pigmented dermal thickenings resembling footpads, ventralized tendons, and ventralized sesamoid bones   (MGI Ref ID J:23922)
• • absent ulna
    • the ulna is often missing or abnormal   (MGI Ref ID J:23922)
  • oligodactyly
    • digit 5 is often missing or abnormal   (MGI Ref ID J:23922)
• reproductive system phenotype
• abnormal oviduct morphology
  • anterior regions of the mutant reproductive tract display a fimbriated, ciliated epithelium typical of the proximal oviduct while posterior regions show a less elaborately folded mucosa composed of a simple columnar epithelium which resembles the isthmic region of the oviduct   (MGI Ref ID J:50342)
  • although regional differentiation occurs along the oviduct, normal elongation and coiling of the oviduct fail to occur   (MGI Ref ID J:50342)
  • no visibly coiled oviducts are present in newborn and adult female mutants   (MGI Ref ID J:50342)
• • short oviduct
    • mutant oviducts are shortened and uncoiled   (MGI Ref ID J:50342)
• abnormal uterus morphology
  • in female mutants, the mesenchymally derived uterine stroma is reduced such that the transverse and circular muscles, which are present but also reduced, lie in proximity to the endometrial epithelium   (MGI Ref ID J:50342)
• • abnormal uterus development
    • both epithelial and mesenchymal differentiation are disrupted in the mutant uterus   (MGI Ref ID J:50342)
  • absent endometrial glands
    • adult female mutants show a nearly complete absence of uterine glands   (MGI Ref ID J:50342)
  • small uterus
    • in female mutants, adult uteri are larger than at the neonatal stages but smaller than those of wild-type females   (MGI Ref ID J:50342)
  • • thin uterus
      • in female mutants, the neonatal uterine wall is thinner and significantly less muscular than that of wild-type females   (MGI Ref ID J:50342)
      • the uterine radial diameter is less than half that of wild-type siblings   (MGI Ref ID J:50342)
      • in contrast, ovarian development is similar to that of wild-type females, as shown by normal follicular growth, ovulation and cycling in the adult   (MGI Ref ID J:50342)
  • thin myometrium
    • in female mutants, the neonatal uterus is significantly less muscular than that of wild-type females   (MGI Ref ID J:50342)
• female infertility
  • mutant females are infertile due to abnormal development of the oviduct and uterus, both of which are Mullerian duct derivatives   (MGI Ref ID J:50342)
  • however, liveborn offspring are obtained from ovaries transplanted to recipient wild-type females   (MGI Ref ID J:50342)
• male infertility
  • adult mutant males are infertile due to the presence of non-regressed Mullerian ducts which prevent the exit of sperm   (MGI Ref ID J:50342)
• skeleton phenotype
• absent ulna
  • the ulna is often missing or abnormal   (MGI Ref ID J:23922)
• embryogenesis phenotype
• abnormal Mullerian duct morphology
  • although Mullerian ducts are present neonatally, the Mullerian duct derivatives of mutant newborn and adult females fail to differentiate properly   (MGI Ref ID J:50342)
  • the lumen of the Mullerian duct is expanded and the Mullerian duct mesenchyme is more condensed than in mice with conditional loss of Ctnnb1 in the Mullerian duct   (MGI Ref ID J:171430)
• • failure of Mullerian duct regression   (MGI Ref ID J:171430)
    • mutant males fail to undergo regression of the Mullerian duct due to absence of the receptor for Mullerian-inhibiting substance   (MGI Ref ID J:50342)
    • non-regressed Mullerian ducts appear as thin, undifferentiated tubes with no regional organization that run alongside the epididymis and the vas deferens from the testis to the urogenital sinus   (MGI Ref ID J:50342)
    • in addition, a second duct appears to prevent the vas deferens from making a proper connection at its distal end   (MGI Ref ID J:50342)
    • however, the testes and Wolffian duct derivatives (epididymis, vas deferens and seminal vesicle) appear normal and mature sperm fill the vas deferens   (MGI Ref ID J:50342)

View Research Applications

Research Applications

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

Wnt7a^tm1Amc related

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Neurodevelopmental Defects

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Wnt7atm1Amc
Allele Name		targeted mutation 1, Andrew P McMahon
Allele Type		Targeted (knock-out)
Common Name(s)		Wnt-7a;
Mutation Made By		Andrew McMahon,   University of Southern California
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		CJ7
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Wnt7a, wingless-related MMTV integration site 7A
Chromosome		6
Gene Common Name(s)		AI849442; Wnt-7a; expressed sequence AI849442; foot-twist; postaxial hemimelia; px; tw;
Molecular Note		A neomycin cassette was inserted into exon 2. Authors state that this is likely a null allele, but present no molecular evidence. [MGI Ref ID J:23922]

Genotyping

Genotyping Information

Genotyping Protocols

Wnt7a^tm1Amc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Parr BA; McMahon AP. 1995. Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature 374(6520):350-3. [PubMed: 7885472]  [MGI Ref ID J:23922]

Additional References

Cygan JA; Johnson RL; McMahon AP. 1997. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development 124(24):5021-32. [PubMed: 9362463]  [MGI Ref ID J:45301]

Hall AC; Lucas FR; Salinas PC. 2000. Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling [see comments] Cell 100(5):525-35. [PubMed: 10721990]  [MGI Ref ID J:60954]

Parr BA; McMahon AP. 1998. Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Nature 395(6703):707-10. [PubMed: 9790192]  [MGI Ref ID J:50342]

Wnt7a^tm1Amc related

Adamska M; Billi AC; Cheek S; Meisler MH. 2005. Genetic interaction between Wnt7a and Lrp6 during patterning of dorsal and posterior structures of the mouse limb. (Erratum: 2005; 233:1614) Dev Dyn 233(2):368-72. [PubMed: 15880584]  [MGI Ref ID J:98369]

Adamska M; MacDonald BT; Sarmast ZH; Oliver ER; Meisler MH. 2004. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol 272(1):134-44. [PubMed: 15242796]  [MGI Ref ID J:92327]

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]

Ashrafi S; Lalancette-Hebert M; Friese A; Sigrist M; Arber S; Shneider NA; Kaltschmidt JA. 2012. Wnt7A Identifies Embryonic gamma-Motor Neurons and Reveals Early Postnatal Dependence of gamma-Motor Neurons on a Muscle Spindle-Derived Signal. J Neurosci 32(25):8725-8731. [PubMed: 22723712]  [MGI Ref ID J:185656]

Carta L; Sassoon D. 2004. Wnt7a is a suppressor of cell death in the female reproductive tract and is required for postnatal and estrogen-mediated growth. Biol Reprod 71(2):444-54. [PubMed: 15070830]  [MGI Ref ID J:91872]

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]

Cygan JA; Johnson RL; McMahon AP. 1997. Novel regulatory interactions revealed by studies of murine limb pattern in Wnt-7a and En-1 mutants. Development 124(24):5021-32. [PubMed: 9362463]  [MGI Ref ID J:45301]

Dabdoub A; Donohue MJ; Brennan A; Wolf V; Montcouquiol M; Sassoon DA; Hseih JC; Rubin JS; Salinas PC; Kelley MW. 2003. Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea. Development 130(11):2375-84. [PubMed: 12702652]  [MGI Ref ID J:82803]

Hall AC; Lucas FR; Salinas PC. 2000. Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling [see comments] Cell 100(5):525-35. [PubMed: 10721990]  [MGI Ref ID J:60954]

Kobayashi A; Shawlot W; Kania A; Behringer RR. 2004. Requirement of Lim1 for female reproductive tract development. Development 131(3):539-49. [PubMed: 14695376]  [MGI Ref ID J:133086]

Kobayashi A; Stewart CA; Wang Y; Fujioka K; Thomas NC; Jamin SP; Behringer RR. 2011. {beta}-Catenin is essential for Mullerian duct regression during male sexual differentiation. Development 138(10):1967-75. [PubMed: 21490063]  [MGI Ref ID J:171430]

Le Grand F; Jones AE; Seale V; Scime A; Rudnicki MA. 2009. Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell 4(6):535-47. [PubMed: 19497282]  [MGI Ref ID J:149821]

Loomis CA; Kimmel RA; Tong CX; Michaud J; Joyner AL. 1998. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Development 125(6):1137-48. [PubMed: 9463360]  [MGI Ref ID J:46971]

Mericskay M; Kitajewski J; Sassoon D. 2004. Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Development 131(9):2061-72. [PubMed: 15073149]  [MGI Ref ID J:89366]

Miller C; Degenhardt K; Sassoon DA. 1998. Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis. Nat Genet 20(3):228-30. [PubMed: 9806537]  [MGI Ref ID J:111222]

Miller C; Sassoon DA. 1998. Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract. Development 125(16):3201-11. [PubMed: 9671592]  [MGI Ref ID J:49656]

Parr BA; McMahon AP. 1998. Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Nature 395(6703):707-10. [PubMed: 9790192]  [MGI Ref ID J:50342]

Stenman JM; Rajagopal J; Carroll TJ; Ishibashi M; McMahon J; McMahon AP. 2008. Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science 322(5905):1247-50. [PubMed: 19023080]  [MGI Ref ID J:142352]

Stump RJ; Ang S; Chen Y; von Bahr T; Lovicu FJ; Pinson K; de Iongh RU; Yamaguchi TP; Sassoon DA; McAvoy JW. 2003. A role for Wnt/beta-catenin signaling in lens epithelial differentiation. Dev Biol 259(1):48-61. [PubMed: 12812787]  [MGI Ref ID J:84052]

Vandenberg AL; Sassoon DA. 2009. Non-canonical Wnt signaling regulates cell polarity in female reproductive tract development via van gogh-like 2. Development 136(9):1559-70. [PubMed: 19363157]  [MGI Ref ID J:147958]

Zhu J; Mackem S. 2011. Analysis of mutants with altered shh activity and posterior digit loss supports a biphasic model for shh function as a morphogen and mitogen. Dev Dyn 240(5):1303-10. [PubMed: 21509901]  [MGI Ref ID J:170964]

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	The resulting mice were crossed at least once to C57BL/6 mice. The strain is maintained as a heterozygote. Homozygotes are viable but not fertile.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	See control note:	Wildtype mice from the colony or B6129SF2/J (Stock # 101045)can be used as controls.
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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See Terms of Use tab for General Terms and Conditions

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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