Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N21pN1   Donating Investigator Eva Eicher,   The Jackson Laboratory

Control Information

	Control
	Wild-type from the colony
	000924 C57BL/6JEiJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Wnt4^tm1Amc allele

002866

129-Wnt4tm1Amc/J

View Strains carrying   Wnt4^tm1Amc     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Wnt4^tm1Amc/Wnt4^tm1Amc

        involves: 129S1/Sv

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:21884)
  • mutants die within 24 hrs of birth
  • mutants are recovered at the expected mendelian frequency at late stages of gestation
  • death is attributed to lack of kidney function
• renal/urinary system phenotype
• abnormal kidney development (MGI Ref ID J:21884)
  • at E15 agenic kidneys consist of undifferentiated mesenchyme interspersed with branches of collecting duct epithelium
• reproductive system phenotype
• abnormal oogenesis (MGI Ref ID J:52554)
  • reduced oocyte development
  • at birth, ovaries have few oocytes and all are degenerating
• abnormal secondary sex determination (MGI Ref ID J:52554)
  • Wolffian duct development and Mullerian duct regression are normal in males but both also occur in mutant females
• secondary sex reversal (MGI Ref ID J:52554)
  • some Wolffian duct development is seen in mutant females proximal sex ducts of chromosomally XX mice appear masculinized at E18.5 and two Wolffian specific duct cell markers, Pax2 and Shh, identify a single ovary-associated duct with a highly convoluted proximal region resembling the epididymal region as a Wolffian duct derivative
  • ectopic expression of Sertoli and Leidig cell marker occurs
  • 3Beta-HSD and 17 alpha-hydroxylase are abnormally expressed in the ovary from E14.5 until birth
  • MIS and Dhh are abnormally expressed in the ovary at birth
  • Mullerian duct development is absent in females at E14.5 and specific Mullerian cell markers, Wnt-7a and Pax-8 are not detected
• hematopoietic system phenotype
• decreased thymocyte number (MGI Ref ID J:75999)
  • at E15-E16, homozygotes show a 20-30% reduction in thymocyte number relative to wild-type embryos
  • however, T cell maturation during fetal development appears unaffected
• immune system phenotype
• decreased thymocyte number (MGI Ref ID J:75999)
  • at E15-E16, homozygotes show a 20-30% reduction in thymocyte number relative to wild-type embryos
  • however, T cell maturation during fetal development appears unaffected

Wnt4^tm1Amc/Wnt4^tm1Amc

        involves: 129/Sv * CD-1

• endocrine/exocrine gland phenotype
• abnormal adenohypophysis morphology (MGI Ref ID J:48144)
  • the anterior pituitary is nearly devoid of all cell types except ACTH-expressing corticotropes
• decreased gonadotroph cell number (MGI Ref ID J:48144)
• decreased somatotroph cell number (MGI Ref ID J:48144)
• decreased thyrotroph cell number (MGI Ref ID J:48144)
• abnormal adrenal gland physiology (MGI Ref ID J:80420)
  • adrenal glands appear morphologically normal but there is reduced aldosterone production in adrenal cortex
  • ectopic expression of adrenal gland- pecific Cyp21 in gonads suggests abnormal migration of adrenal cells in early development
• nervous system phenotype
• abnormal adenohypophysis morphology (MGI Ref ID J:48144)
  • the anterior pituitary is nearly devoid of all cell types except ACTH-expressing corticotropes
• decreased gonadotroph cell number (MGI Ref ID J:48144)
• decreased somatotroph cell number (MGI Ref ID J:48144)
• decreased thyrotroph cell number (MGI Ref ID J:48144)

Wnt4^tm1Amc/Wnt4^tm1Amc

        involves: 129/Sv * C57BL/6

• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:98831)
  • severely hypoplastic metanephroi, that can form a few glomeruli, nephron tubules and medulla-like structures

View Research Applications

Research Applications

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

Wnt4^tm1Amc related

Developmental Biology Research
Internal/Organ Defects (kidney)

Internal/Organ Research
Kidney Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Wnt4tm1Amc
Allele Name		targeted mutation 1, Andrew P McMahon
Allele Type		Targeted (knock-out)
Common Name(s)		Wnt-4-; Wnt4n;
Mutation Made By		Andrew McMahon,   Harvard University
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		Wnt4, wingless-related MMTV integration site 4
Chromosome		4
Gene Common Name(s)		MGC112773; SERKAL; WNT-4; Wnt-4;
Molecular Note		Exon 3, encoding amino acids 106 through 196, was replaced by a PGK-neo cassette. The occasional expression of the targeted locus was observed in poorly developed aggregates in the kidneys of homozygous mutant mice via in situ hybridization. Expression was unaltered in the central nervous system and mesonephric mesenchyme. [MGI Ref ID J:21884]

Genotyping

Genotyping Information

Genotyping Protocols

Wnt4^tm1Amc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Stark K; Vainio S; Vassileva G; McMahon AP. 1994. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372(6507):679-83. [PubMed: 7990960]  [MGI Ref ID J:21884]

Additional References

Wnt4^tm1Amc related

Chassot AA; Ranc F; Gregoire EP; Roepers-Gajadien HL; Taketo MM; Camerino G; de Rooij DG; Schedl A; Chaboissier MC. 2008. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet 17(9):1264-77. [PubMed: 18250098]  [MGI Ref ID J:133933]

Coveney D; Ross AJ; Slone JD; Capel B. 2007. A microarray analysis of the XX Wnt4 mutant gonad targeted at the identification of genes involved in testis vascular differentiation.(Correction: 2008; 8:529-537) Gene Expr Patterns 7(1-2):82-92. [PubMed: 16844427]  [MGI Ref ID J:116022]

Heikkila M; Peltoketo H; Leppaluoto J; Ilves M; Vuolteenaho O; Vainio S. 2002. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143(11):4358-65. [PubMed: 12399432]  [MGI Ref ID J:80420]

Heikkila M; Prunskaite R; Naillat F; Itaranta P; Vuoristo J; Leppaluoto J; Peltoketo H; Vainio S. 2005. The partial female to male sex reversal in Wnt-4-deficient females involves induced expression of testosterone biosynthetic genes and testosterone production, and depends on androgen action. Endocrinology 146(9):4016-23. [PubMed: 15932923]  [MGI Ref ID J:129451]

Itaranta P; Chi L; Seppanen T; Niku M; Tuukkanen J; Peltoketo H; Vainio S. 2006. Wnt-4 signaling is involved in the control of smooth muscle cell fate via Bmp-4 in the medullary stroma of the developing kidney. Dev Biol 293(2):473-83. [PubMed: 16546160]  [MGI Ref ID J:108713]

Jeays-Ward K; Dandonneau M; Swain A. 2004. Wnt4 is required for proper male as well as female sexual development. Dev Biol 276(2):431-40. [PubMed: 15581876]  [MGI Ref ID J:106304]

Jeays-Ward K; Hoyle C; Brennan J; Dandonneau M; Alldus G; Capel B; Swain A. 2003. Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development 130(16):3663-70. [PubMed: 12835383]  [MGI Ref ID J:84602]

Kim Y; Kobayashi A; Sekido R; DiNapoli L; Brennan J; Chaboissier MC; Poulat F; Behringer RR; Lovell-Badge R; Capel B. 2006. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4(6):e187. [PubMed: 16700629]  [MGI Ref ID J:110252]

Kispert A; Vainio S; Shen L; Rowitch DH; McMahon AP. 1996. Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips. Development 122(11):3627-37. [PubMed: 8951078]  [MGI Ref ID J:36828]

Kobayashi A; Kwan KM; Carroll TJ; McMahon AP; Mendelsohn CL; Behringer RR. 2005. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 132(12):2809-23. [PubMed: 15930111]  [MGI Ref ID J:98831]

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]

Louis I; Heinonen KM; Chagraoui J; Vainio S; Sauvageau G; Perreault C. 2008. The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling. Immunity 29(1):57-67. [PubMed: 18617424]  [MGI Ref ID J:137842]

Maatouk DM; DiNapoli L; Alvers A; Parker KL; Taketo MM; Capel B. 2008. Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet 17(19):2949-55. [PubMed: 18617533]  [MGI Ref ID J:138861]

Mulroy T; McMahon JA; Burakoff SJ; McMahon AP; Sen J. 2002. Wnt-1 and Wnt-4 regulate thymic cellularity. Eur J Immunol 32(4):967-71. [PubMed: 11920562]  [MGI Ref ID J:75999]

Ottolenghi C; Pelosi E; Tran J; Colombino M; Douglass E; Nedorezov T; Cao A; Forabosco A; Schlessinger D. 2007. Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells. Hum Mol Genet 16(23):2795-804. [PubMed: 17728319]  [MGI Ref ID J:129972]

Park JS; Valerius MT; McMahon AP. 2007. Wnt/{beta}-catenin signaling regulates nephron induction during mouse kidney development. Development 134(13):2533-9. [PubMed: 17537789]  [MGI Ref ID J:122521]

Perantoni AO; Timofeeva O; Naillat F; Richman C; Pajni-Underwood S; Wilson C; Vainio S; Dove LF; Lewandoski M. 2005. Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development 132(17):3859-71. [PubMed: 16049111]  [MGI Ref ID J:101175]

Potok MA; Cha KB; Hunt A; Brinkmeier ML; Leitges M; Kispert A; Camper SA. 2008. WNT signaling affects gene expression in the ventral diencephalon and pituitary gland growth. Dev Dyn 237(4):1006-20. [PubMed: 18351662]  [MGI Ref ID J:132979]

Saitoh A; Hansen LA; Vogel JC; Udey MC. 1998. Characterization of Wnt gene expression in murine skin: possible involvement of epidermis-derived Wnt-4 in cutaneous epithelial-mesenchymal interactions. Exp Cell Res 243(1):150-60. [PubMed: 9716459]  [MGI Ref ID J:49458]

Spater D; Hill TP; O'sullivan RJ; Gruber M; Conner DA; Hartmann C. 2006. Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis. Development 133(15):3039-49. [PubMed: 16818445]  [MGI Ref ID J:119030]

Treier M; Gleiberman AS; O'Connell SM; Szeto DP; McMahon JA; McMahon AP; Rosenfeld MG. 1998. Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev 12(11):1691-704. [PubMed: 9620855]  [MGI Ref ID J:48144]

Vainio S; Heikkila M; Kispert A; Chin N; McMahon AP. 1999. Female development in mammals is regulated by Wnt-4 signalling. Nature 397(6718):405-9. [PubMed: 9989404]  [MGI Ref ID J:52554]

Valerius MT; McMahon AP. 2008. Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed during nephron formation. Gene Expr Patterns 8(5):297-306. [PubMed: 18346943]  [MGI Ref ID J:133949]

Yao HH; Aardema J; Holthusen K. 2006. Sexually dimorphic regulation of inhibin Beta B in establishing gonadal vasculature in mice. Biol Reprod 74(5):978-83. [PubMed: 16452457]  [MGI Ref ID J:107812]

Yao HH; Matzuk MM; Jorgez CJ; Menke DB; Page DC; Swain A; Capel B. 2004. Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis. Dev Dyn 230(2):210-5. [PubMed: 15162500]  [MGI Ref ID J:90277]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000924 C57BL/6JEiJ
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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

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For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.