Description

Strain Information

Former Names 129-Wlstm1.1Lan/J    (Changed: 11-JUN-12 ) Type Coisogenic; Mutant Stock; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   12-AUG-11 Species laboratory mouse Generation F?+N1F6 (30-JUN-11) Generation Definitions   Donating Investigator Richard A. Lang,   Cincinnati Children's Hospital

Description
These Wls floxed mutant mice possess loxP site before the ATG start site in the 5' untranslated region of exon 1 and another upstream of exon 2 of the wntless homolog (Drosophila) (Wls) gene. Mice that are homozygous for this allele are viable, fertile, and normal in size. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 1 deleted in cre-expressing tissues, abolishing gene function. When bred to a strain expressing Cre recombinase in the germline, homozygotes fail to develop mesoderm and are embryonic lethal by E8.5. When bred to a strain expressing Cre recombinase in pancreatic precursors, the mutant mice develop pancreatic hypoplasia. When bred to a strain expressing Cre recombinase in neural crest cells, the mutant mouse strain has severe brain malformations and exhibit postnatal lethality. This mutant mouse strain is useful to study Wnt signaling in any organ or tissue that can be targeted with a Cre recombinase.

Development
A targeting vector was designed to insert a loxP site upstream of the ATG start site in exon 1, followed by an frt-flanked neomycin resistance (neo) cassette and a second loxP site upstream of exon 2 of the wntless homolog (Drosophila) (Wls) gene. The construct was electroporated into 129SvEv-derived "Duffy" embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to mice on a 129 background. Offspring, carrying this floxed-Wls allele, were bred with Flp transgenic mice on a 129 background to delete the neo cassette, and progeny were crossed to remove the frt-flanked transgene, resulting in a colony homozygous for the floxed-Wls allele. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation to establish the colony.

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

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.
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Tg(EIIa-cre)C5379Lmgd/0 Wls^tm1.1Lan/Wls^tm1.1Lan

        involves: 129S/SvEv * FVB/N * SJL   (conditional)

• mortality/aging
• partial embryonic lethality between implantation and somite formation
  • at E8.5, 9 of 10 embryos are in the process of being reabsorbed   (MGI Ref ID J:164701)
• embryogenesis phenotype
• embryonic growth arrest
  • germline homozygotes appear arrested at E6, they do not progress past the egg cylinder stage, and by morphological criteria lack mesoderm   (MGI Ref ID J:164701)
• failure of primitive streak formation   (MGI Ref ID J:164701)

Tg(Ipf1-cre)6Tuv/0 Wls^tm1.1Lan/Wls^tm1.1Lan

        involves: 129S/SvEv * FVB/N * SJL   (conditional)

• endocrine/exocrine gland phenotype
• pancreas hypoplasia   (MGI Ref ID J:164701)

Tg(Wnt1-cre)11Rth/0 Wls^tm1.1Lan/Wls^tm1.1Lan

        involves: 129S/SvEv * C57BL/6J * CBA/J * SJL   (conditional)

• mortality/aging
• perinatal lethality   (MGI Ref ID J:164701)
• embryogenesis phenotype
• abnormal neural tube morphology/development
  • The mutant phenotype was obvious as early as E9.5 due to the presence of a shortened neural tube   (MGI Ref ID J:164701)
• abnormal rostral-caudal axis patterning
  • mutant mice exhibit a shortened anteroposterior axis and no apparent isthmus   (MGI Ref ID J:164701)
• nervous system phenotype
• abnormal forebrain morphology
  • at E12.5 a severely truncated forebrain   (MGI Ref ID J:164701)
• abnormal metencephalon morphology
  • at E10.5 verified deletion of regions of the metencephalon   (MGI Ref ID J:164701)
• • absent cerebellum
    • at E12.5   (MGI Ref ID J:164701)
• abnormal midbrain morphology
  • absent midbrain   (MGI Ref ID J:164701)
• abnormal neural tube morphology/development
  • The mutant phenotype was obvious as early as E9.5 due to the presence of a shortened neural tube   (MGI Ref ID J:164701)
• absent choroid plexus
  • at E12.5   (MGI Ref ID J:164701)

View Research Applications

Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      brain

Endocrine Deficiency Research
Pancreas Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Wlstm1.1Lan
Allele Name		targeted mutation 1.1, Richard A Lang
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Wlsflox;
Strain of Origin		129S6/SvEvTac
Gene Symbol and Name		Wls, wntless homolog (Drosophila)
Chromosome		3
Gene Common Name(s)		5031439A09Rik; AI173978; AI987742; C1orf139; EVI; G protein-coupled receptor 177; GPR177; Gpr177; MRP; RIKEN cDNA 5031439A09 gene; expressed sequence AI173978; expressed sequence AI987742; mig-14;
Molecular Note		A targeting vector was designed to insert a loxP site upstream of the coding sequence in exon 1, followed by an frt-flanked neomycin resistance (neo) cassette and a second loxP site upstream of exon 2 of the wntless homolog (Drosophila) (Wls) gene. Flp mediated recombination removed the neo cassette leaving the coding sequence of exon 1 floxed. [MGI Ref ID J:164701]

Genotyping

Genotyping Information

Genotyping Protocols

Wls^tm1.1Lan, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Carpenter AC; Rao S; Wells JM; Campbell K; Lang RA. 2010. Generation of mice with a conditional null allele for Wntless. Genesis 48(9):554-8. [PubMed: 20614471]  [MGI Ref ID J:164701]

Additional References

Wls^tm1.1Lan related

Chen D; Jarrell A; Guo C; Lang R; Atit R. 2012. Dermal beta-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development 139(8):1522-33. [PubMed: 22434869]  [MGI Ref ID J:183485]

Stefater JA 3rd; Lewkowich I; Rao S; Mariggi G; Carpenter AC; Burr AR; Fan J; Ajima R; Molkentin JD; Williams BO; Wills-Karp M; Pollard JW; Yamaguchi T; Ferrara N; Gerhardt H; Lang RA. 2011. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature 474(7352):511-5. [PubMed: 21623369]  [MGI Ref ID J:173385]

Stefater JA 3rd; Rao S; Bezold K; Aplin AC; Nicosia RF; Pollard JW; Ferrara N; Lang RA. 2013. Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound angiogenesis and repair. Blood 121(13):2574-8. [PubMed: 23303818]  [MGI Ref ID J:195441]

Zhong Z; Zylstra-Diegel CR; Schumacher CA; Baker JJ; Carpenter AC; Rao S; Yao W; Guan M; Helms JA; Lane NE; Lang RA; Williams BO. 2012. Wntless functions in mature osteoblasts to regulate bone mass. Proc Natl Acad Sci U S A 109(33):E2197-204. [PubMed: 22745162]  [MGI Ref ID J:188416]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   12-AUG-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
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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