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

Former Names B6.129X1-Wnt7btm2Amc/J    (Changed: 30-MAR-09 ) B6.129X1(Cg)-Wnt7btm2Amc/J    (Changed: 14-NOV-08 ) Type Congenic; Mutant Stock; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Andrew P McMahon,   University of Southern California

Description
Mice homozygous for the Wnt7b^c3 allele are viable and fertile, with loxP sites flanking exon 3 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have this region deleted in the cre-expressing tissue(s). Unlike other Wnt7b mutant alleles, this Wnt7b^c3 conditional allele is not affected by alternative exon 1 splicing. These Wnt7b^c3 mice may be useful in generating conditional mutations for studying the role of Wnt7b (and other Wnt family members) in development and canonical Wnt signaling cascades, including lung differentiation and growth. In addition, these mice may also be useful in conjunction with other Wnt7 mutant strains including Wnt7b knockout mice (Stock No. 004693) and Wnt7a mutant mice (Stock No. 004715).

When bred to a strain expressing Cre recombinase in epiblast cells (see Stock No. 008454, 004783 for example), this mutant mouse strain may be useful in studies of embronic lung growth.

When bred to a strain expressing Cre recombinase in the mesonephric duct and its' developmental derivatives (see Stock No. 004692 for example), this mutant mouse strain may be useful in studies of kidney development.

Development
A targeting vector was designed to insert loxP sites on both sides of exon 3 of the targeted gene, as well as insert an frt-flanked PGK-neo cassette downstream of exon 3. The donating investigator reports that this construct was microinjected into 129X1/SvJ-derived AV3 embryonic stem (ES) cells, correctly targeted ES cells were injected into recipient blastocysts, and chimeric mice were bred with C57BL/6 mice. The resulting Wnt7b^c3 mutant mice were next backcrossed to C57BL/6 mice for a few generations (and confirmed to still harbor the frt-flanked PGK-neo cassette downstream of exon 3) prior to arrival at The Jackson Laboratory. Upon arrival, these mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony. It was then determined that these mice are on a mixed C57BL/6J and 129X1/SvJ genetic background.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Wnt7b

004693

B6;129-Wnt7btm1Parr/J

View Strains carrying other alleles of Wnt7b     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Gt(ROSA)26Sor^tm1Sor/? Wnt7b^tm2Amc/Wnt7b^tm2.1Amc Tg(Hoxb7-cre)13Amc/0

        involves: 129S4/SvJaeSor * 129X1/SvJ * C57BL/6   (conditional)

• renal/urinary system phenotype
• dilated kidney collecting duct
  • at E15.5 the collecting ducts are dilated and branch points are less evident   (MGI Ref ID J:142685)

Wnt7b^tm2Amc/Wnt7b^tm2.1Amc Tg(Hoxb7-cre)13Amc/0

        involves: 129X1/SvJ * C57BL/6   (conditional)

• mortality/aging
• complete postnatal lethality
  • survive to P11 - P12   (MGI Ref ID J:142685)
• renal/urinary system phenotype
• abnormal kidney morphology
  • at P11 - P12 kidneys are grossly abnormal   (MGI Ref ID J:142685)
• • absent kidney medulla
    • absent at P10   (MGI Ref ID J:142685)
• decreased urine osmolality
  • at P10, urine osmolality is 56% that of controls   (MGI Ref ID J:142685)
• kidney failure
  • by P11 - P12 kidneys are physiologically incompetent   (MGI Ref ID J:142685)
• homeostasis/metabolism phenotype
• decreased urine osmolality
  • at P10, urine osmolality is 56% that of controls   (MGI Ref ID J:142685)

Wnt7b^tm2Amc/Wnt7b^tm2.1Amc Tg(Sox2-cre)1Amc/0

        involves: 129X1/SvJ * C57BL/6 * CBA   (conditional)

• mortality/aging
• complete neonatal lethality
  • mice die within hours of birth   (MGI Ref ID J:134483)
• respiratory system phenotype
• abnormal lung development
  • lung epithelial and mesenchyme tip cell progenitors exhibit decreased replication compared to in wild-type mice   (MGI Ref ID J:134483)
  • however, normal cell differentiation and patterning are preserved   (MGI Ref ID J:134483)
• • decreased mesenchymal cell proliferation involved in lung development
    • mesenchyme tip cell progenitors exhibit decreased replication compared to in wild-type mice   (MGI Ref ID J:134483)
  • thin lung-associated mesenchyme
    • the lung mesenchyme is thinner than in wild-type mice   (MGI Ref ID J:134483)
• abnormal right lung middle lobe morphology
  • the medial lobe bronchus of the right lung emanates from the cephalic lobe bronchus, unlike in wild-type mice   (MGI Ref ID J:134483)
  • however, the correct number of lobes is formed   (MGI Ref ID J:134483)
• abnormal tracheal cartilage morphology
  • cartilaginous rings are incomplete   (MGI Ref ID J:134483)
• atelectasis
  • lungs are poorly inflated   (MGI Ref ID J:134483)
• lung hemorrhage   (MGI Ref ID J:134483)
• small lung
  • at E12.5   (MGI Ref ID J:134483)
• • decreased lung weight
    • lung weight is 50% of wild-type at E18.5 and 25% of wild-type at E14.5   (MGI Ref ID J:134483)
• homeostasis/metabolism phenotype
• cyanosis
  • after birth mice become cyanotic despite chest wall movements   (MGI Ref ID J:134483)
• renal/urinary system phenotype
• abnormal kidney cell proliferation
  • at E15.5, the majority of cells in the collecting duct divide along the radial axis unlike in controls where the majority of cells divide along the longitudinal axis   (MGI Ref ID J:142685)
• • decreased kidney cell proliferation
    • cell proliferation in the loop of Henle is significantly reduced   (MGI Ref ID J:142685)
• abnormal kidney morphology
  • renal corpuscles abut the renal pelvis   (MGI Ref ID J:142685)
  • despite the absence of the medulla, kidneys are similar in size to controls   (MGI Ref ID J:142685)
• • abnormal kidney collecting duct epithelium morphology
    • at E15.5, the majority of cells in the collecting duct divide along the radial axis unlike in controls where the majority of cells divide along the longitudinal axis   (MGI Ref ID J:142685)
    • at E17.5, a marked increase in the rate of apoptosis is seen in distal collecting duct epithelial cells   (MGI Ref ID J:142685)
  • abnormal kidney medulla development
    • at E15.5 and E16.5, the nascent medulla is absent indicating a failure to initiate medulla formation   (MGI Ref ID J:142685)
  • absent kidney medulla
    • absent at E18.5   (MGI Ref ID J:142685)
  • truncated loop of Henle
    • at E18.5 the loop of Henle is truncated resembling morphology at an earlier stage prior to loop elongation   (MGI Ref ID J:142685)
    • cell proliferation in the loop of Henle is significantly reduced   (MGI Ref ID J:142685)
• hydroureter
  • at E18.5, less than a third of mice show hydroureter like swelling of the pelvic region   (MGI Ref ID J:142685)
• increased kidney apoptosis
  • at E17.5, a marked increase in the rate of apoptosis is seen in distal collecting duct epithelial cells   (MGI Ref ID J:142685)
• skeleton phenotype
• abnormal tracheal cartilage morphology
  • cartilaginous rings are incomplete   (MGI Ref ID J:134483)
• cardiovascular system phenotype
• lung hemorrhage   (MGI Ref ID J:134483)
• cellular phenotype
• abnormal kidney cell proliferation
  • at E15.5, the majority of cells in the collecting duct divide along the radial axis unlike in controls where the majority of cells divide along the longitudinal axis   (MGI Ref ID J:142685)
• • decreased kidney cell proliferation
    • cell proliferation in the loop of Henle is significantly reduced   (MGI Ref ID J:142685)
• decreased mesenchymal cell proliferation involved in lung development
  • mesenchyme tip cell progenitors exhibit decreased replication compared to in wild-type mice   (MGI Ref ID J:134483)
• increased kidney apoptosis
  • at E17.5, a marked increase in the rate of apoptosis is seen in distal collecting duct epithelial cells   (MGI Ref ID J:142685)

View Research Applications

Research Applications

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

Cell Biology Research
Signal Transduction

Developmental Biology Research
Internal/Organ Defects
      lung

Internal/Organ Research
Lung Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Wnt7btm2Amc
Allele Name		targeted mutation 2, Andrew P McMahon
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Wnt7bC3;
Mutation Made By		Andrew McMahon,   University of Southern California
Strain of Origin		129X1/SvJ
ES Cell Line Name		AV3
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Wnt7b, wingless-related MMTV integration site 7B
Chromosome		15
Gene Common Name(s)		Wnt-7b;
Molecular Note		Exon 3 was floxed and an frt flanked PGK-neo cassette was inserted downstream of exon 3. [MGI Ref ID J:134483]

Genotyping

Genotyping Information

Genotyping Protocols

Wnt7b^tm2Amc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Rajagopal J; Carroll TJ; Guseh JS; Bores SA; Blank LJ; Anderson WJ; Yu J; Zhou Q; McMahon AP; Melton DA. 2008. Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme. Development 135(9):1625-34. [PubMed: 18367557]  [MGI Ref ID J:134483]

Additional References

Wnt7b^tm2Amc related

Gordon EJ; Rao S; Pollard JW; Nutt SL; Lang RA; Harvey NL. 2010. Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation. Development 137(22):3899-910. [PubMed: 20978081]  [MGI Ref ID J:167063]

Lin SL; Li B; Rao S; Yeo EJ; Hudson TE; Nowlin BT; Pei H; Chen L; Zheng JJ; Carroll TJ; Pollard JW; McMahon AP; Lang RA; Duffield JS. 2010. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A 107(9):4194-9. [PubMed: 20160075]  [MGI Ref ID J:158579]

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]

Tu X; Joeng KS; Nakayama KI; Nakayama K; Rajagopal J; Carroll TJ; McMahon AP; Long F. 2007. Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell 12(1):113-27. [PubMed: 17199045]  [MGI Ref ID J:117333]

Yu J; Carroll TJ; Rajagopal J; Kobayashi A; Ren Q; McMahon AP. 2009. A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney. Development 136(1):161-71. [PubMed: 19060336]  [MGI Ref ID J:142685]

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
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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