Strain Name:

B6.129-Tnfsf11tm1.1Caob/J

Stock Number:

018978

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Availability:

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These RANKLf/f mice are a floxed strain that may be useful for studying bone development and regeneration.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
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Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   22-MAY-13
Specieslaboratory mouse
GenerationN9pN1+F1 (11-MAR-13)
Generation Definitions
 
Donating Investigator Charles O'Brien,   University of Arkansas for Medical Scien

Description
These RANKLf/f mutant mice possess loxP sites flanking exons 3-4 of the tumor necrosis factor (ligand) superfamily, member 11 (Tnfsf11) gene. Tnfsf11 encodes the cytokine RANKL, a ligand for RANK, both of which are essential for osteoclast differentiation, development, function and survival. RANKL is expressed in chondrocytes and osteocytes embedded in the bone matrix where it controls mineralized cartilage resorption, bone remodeling, and bone loss. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissue(s).

For example, when bred to B6.Cg-Tg(Prrx1-cre)1Cjt/J mice (Stock No. 005584) expressing Cre recombinase in the developing limbs and parts of the skull, double mutant mice had increased bone mineral density and cancellous bone volume.

When bred to B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J mice (Stock No. 006361) expressing Cre recombinase under the control of the tetracycline analog doxycycline, EGFP-Cre fusion protein expression is restricted to the osteoblast lineage. In the absence of doxycycline, Cre expression results in altered bone mineral density, bone volume and cartilage.

When bred to a strain carrying Tg(BGLAP-cre)1Clem (Stock No. 019509), Cre recombinase expression in osteoblasts results in increased bone mineral density, increased trabecular volume, and abnormal cartilage.

When crossed to B6N.FVB-Tg(Dmp1-cre)1Jqfe/BwdJ (see Stock No. 023047) Cre recombinase expression in odontoblasts and osteocytes, results in increased bone mineral density, decreased compact bone thickness, increased trabecular bone volume and decreased numbers of osteoclasts.

Development
A targeting vector was designed to insert a frt-flanked PGK-neo cassette followed by a loxP site upstream of exon 3, and a second loxP site just downstream of exon 4 of the tumor necrosis factor (ligand) superfamily, member 11 (Tnfsf11) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to C57BL/6 females. Offspring were bred with 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J mice (Stock No. 003946) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. The resulting homozygous RANKLf/f mice were backcrossed to C57BL/6 mice for at least 9 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

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.
Osteopetrosis, Autosomal Recessive 2; OPTB2   (TNFSF11)
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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Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob Tg(BGLAP-cre)1Clem/0

        involves: 129S * 129X1/SvJ * C57BL/6 * FVB/NJ   (conditional)
  • skeleton phenotype
  • abnormal cartilage morphology
    • mice exhibit unresorbed cartilage unlike wild-type mice   (MGI Ref ID J:177558)
    • increased long bone epiphyseal plate size
      • widened growth plate in the femur   (MGI Ref ID J:177558)
  • increased bone mineral density
    • at 5 weeks of age   (MGI Ref ID J:177558)
  • increased trabecular bone volume
    • at 5 weeks of age   (MGI Ref ID J:177558)
  • craniofacial phenotype
  • failure of tooth eruption
  • growth/size/body phenotype
  • failure of tooth eruption

Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob Tg(Dmp1-cre)1Jqfe/0

        involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * FVB   (conditional)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • mice exhibit normal tooth eruption and growth plates   (MGI Ref ID J:177558)
    • abnormal bone structure
      • mice suspended by their tails for 3 weeks are protected from loss of bone and changes in cancellous architecture compared with similarly treated wild-type mice   (MGI Ref ID J:177558)
      • abnormal osteoclast cell number
        • mice suspended by their tails for 3 weeks do not exhibit an increase in osteoclast number compared with similarly treated wild-type mice   (MGI Ref ID J:177558)
        • decreased osteoclast cell number   (MGI Ref ID J:177558)
      • abnormal trabecular bone morphology
        • mice suspended by their tails for 3 weeks exhibit increased trabecular spacing compared with similarly treated wild-type mice   (MGI Ref ID J:177558)
        • increased trabecular bone volume
          • at 6 months of age in the femur and spine   (MGI Ref ID J:177558)
      • decreased compact bone thickness
        • in mice suspended by their tails for 3 weeks   (MGI Ref ID J:177558)
      • increased bone mineral density
        • progressively in the femur and spine   (MGI Ref ID J:177558)
  • immune system phenotype
  • abnormal osteoclast cell number
    • mice suspended by their tails for 3 weeks do not exhibit an increase in osteoclast number compared with similarly treated wild-type mice   (MGI Ref ID J:177558)
    • decreased osteoclast cell number   (MGI Ref ID J:177558)
  • hematopoietic system phenotype
  • abnormal osteoclast cell number
    • mice suspended by their tails for 3 weeks do not exhibit an increase in osteoclast number compared with similarly treated wild-type mice   (MGI Ref ID J:177558)
    • decreased osteoclast cell number   (MGI Ref ID J:177558)

Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob Tg(Prrx1-cre)1Cjt/0

        involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6   (conditional)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • mice exhibit normal bone mass and tooth eruption   (MGI Ref ID J:177558)
    • abnormal cartilage morphology
      • mice exhibit unresorbed cartilage unlike wild-type mice   (MGI Ref ID J:177558)
      • increased long bone epiphyseal plate size
        • widened growth plate in the femur   (MGI Ref ID J:177558)
    • decreased osteoclast cell number
      • absent in femur   (MGI Ref ID J:177558)
    • increased bone mineral density   (MGI Ref ID J:177558)
    • increased trabecular bone volume
      • in the femur but not the spine   (MGI Ref ID J:177558)
    • osteopetrosis
  • immune system phenotype
  • decreased osteoclast cell number
    • absent in femur   (MGI Ref ID J:177558)
  • hematopoietic system phenotype
  • decreased osteoclast cell number
    • absent in femur   (MGI Ref ID J:177558)

Tnfsf11tm1.1Caob/Tnfsf11tm1.1Caob Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0

        involves: 129S * 129X1/SvJ * C57BL/6 * CD-1   (conditional)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • mice treated with doxycycline until 4 months of age exhibit normal cancellous architecture at 6 months   (MGI Ref ID J:177558)
    • abnormal cartilage morphology
      • mice exhibit unresorbed cartilage unlike wild-type mice   (MGI Ref ID J:177558)
      • increased long bone epiphyseal plate size
        • widened growth plate in the femur   (MGI Ref ID J:177558)
    • increased bone mineral density
      • at 5 weeks of age   (MGI Ref ID J:177558)
    • increased trabecular bone volume
      • at 5 weeks of age   (MGI Ref ID J:177558)
  • craniofacial phenotype
  • failure of tooth eruption
    • in all mice   (MGI Ref ID J:177558)
    • however, exposure to doxycycline restores tooth eruption   (MGI Ref ID J:177558)
  • growth/size/body phenotype
  • failure of tooth eruption
    • in all mice   (MGI Ref ID J:177558)
    • however, exposure to doxycycline restores tooth eruption   (MGI Ref ID J:177558)
View Research Applications

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

Developmental Biology Research
Skeletal Defects
      osteopetrosis

Internal/Organ Research
Skeleton
      Bone

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tnfsf11tm1.1Caob
Allele Name targeted mutation 1.1, Charles O'Brien
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) RANKLf;
Mutation Made By Charles O'Brien,   University of Arkansas for Medical Scien
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Tnfsf11, tumor necrosis factor (ligand) superfamily, member 11
Chromosome 14
Gene Common Name(s) CD254; Ly109l; ODF; OPGL; OPTB2; RANKL; TNF-related activation-induced cytokine; TRANCE; Trance; hRANKL2; osteoclast differentiation factor; sOdf;
Molecular Note An FRT-flanked neo cassette with a 5' loxP site was inserted upstream of exon 3. An additional loxP site was inserted downstream of exon 4. Flp-mediated recombination removed the neo cassette and left exons 3 and 4 floxed. [MGI Ref ID J:177558]

Genotyping

Genotyping Information

Genotyping Protocols

Tnfsf11tm1.1Caob, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Xiong J; Onal M; Jilka RL; Weinstein RS; Manolagas SC; O'Brien CA. 2011. Matrix-embedded cells control osteoclast formation. Nat Med 17(10):1235-41. [PubMed: 21909103]  [MGI Ref ID J:177558]

Additional References

Tnfsf11tm1.1Caob related

Onal M; Xiong J; Chen X; Thostenson JD; Almeida M; Manolagas SC; O'Brien CA. 2012. Receptor activator of nuclear factor kappaB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J Biol Chem 287(35):29851-60. [PubMed: 22782898]  [MGI Ref ID J:190415]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   22-MAY-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Tnfsf11tm1.1Caob  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Tnfsf11tm1.1Caob x Homozygous for Tnfsf11tm1.1Caob  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Tnfsf11tm1.1Caob  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Tnfsf11tm1.1Caob x Homozygous for Tnfsf11tm1.1Caob  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

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

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