Strain Name:

129S.129-Bbs4tm1Vcs/J

Stock Number:

010752

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These Bbs4 targeted mutation mice have phenotypes associated with a selective lack of cilia formation or function. Homozygotes exhibit obesity (cause unknown), retinal degeneration, and male infertility. This strain may be useful as a model for some features of Bardet-Biedl syndrome.

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 Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Val Sheffield,   University of Iowa, HHMI

Description
These targeted mutation mice have phenotypes associated with a selective lack of cilia formation or function. Homozygotes weigh less than their littermates at 3 weeks of age, but for unknown reasons become obese over time. Retinal degeneration begins at birth and continues until the entire photoreceptor cell layer is ablated at about 7 months of age. Sperm never develop flagella, causing male infertility. Northern blot analysis confirms that expression of the targeted gene is eliminated in eyes, brain, kidney, ovary, liver, spleen, heart, lungs, and muscle.

Development
Exons 6-11 were replaced with a neomycin resistance cassette using (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. This strain was backcrossed seven times to 129/SvEv by the donating laboratory.

Related Strains

Strains carrying   Bbs4tm1Vcs allele
010728   B6.129-Bbs4tm1Vcs/J
View Strains carrying   Bbs4tm1Vcs     (1 strain)

Strains carrying other alleles of Bbs4
024661   B6N(Cg)-Bbs4tm1b(EUCOMM)Hmgu/J
View Strains carrying other alleles of Bbs4     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Bardet-Biedl Syndrome 4; BBS4
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Bardet-Biedl Syndrome 1; BBS1   (BBS4)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Bbs4tm1Vcs/Bbs4tm1Vcs

        involves: 129S1/Sv * 129X1/SvJ
  • behavior/neurological phenotype
  • abnormal placing response
    • when lowered towards a wire grid females show less forelimb paddling   (MGI Ref ID J:94467)
  • decreased aggression
    • mutants are more submissive towards other mice compared to wild-type controls   (MGI Ref ID J:94467)
  • decreased grip strength
    • mutants are unable to grip a wire grid with the hindlimbs when lifted by the tail   (MGI Ref ID J:94467)
  • hyporesponsive to tactile stimuli
    • mutants are less sensitive to touch and are not vocal during handling   (MGI Ref ID J:94467)
  • endocrine/exocrine gland phenotype
  • decreased salivation
    • no salivation is seen when mutants bite on a dowel   (MGI Ref ID J:94467)
  • taste/olfaction phenotype
  • abnormal olfaction
    • mutants are less able to find hidden food   (MGI Ref ID J:94467)
  • nervous system phenotype
  • abnormal basal ganglion morphology
    • reduction in size of the corpus striatum at 3-weeks and 3.5- to 6-months of age   (MGI Ref ID J:128532)
  • enlarged lateral ventricles
    • enlarged at 3.5- to 6-months of age   (MGI Ref ID J:128532)
  • enlarged third ventricle
    • enlarged at 3.5- to 6-months of age   (MGI Ref ID J:128532)
  • small hippocampus
    • reduced in size at 3.5- to 6-months of age   (MGI Ref ID J:128532)
  • thin cerebral cortex
    • thinning of the caudal half detected at 3.5- to 6-months of age   (MGI Ref ID J:128532)
  • digestive/alimentary phenotype
  • decreased salivation
    • no salivation is seen when mutants bite on a dowel   (MGI Ref ID J:94467)
  • integument phenotype
  • hyporesponsive to tactile stimuli
    • mutants are less sensitive to touch and are not vocal during handling   (MGI Ref ID J:94467)
  • renal/urinary system phenotype
  • abnormal renal tubule epithelial cell primary cilium morphology
    • at 3-4 months of age, the average length of mutant renal tubule primary cilia is significantly increased relative to that in wild-type kidneys   (MGI Ref ID J:137093)
    • in culture, wild-type renal tubule epithelial cells of mostly of collecting duct origin maintain a constant ciliary length between days 7 and 10, whereas mutant cilia display an initial delay but surpass the length of wild-type cilia by 10 days   (MGI Ref ID J:137093)
    • however, no differences in the cellular composition or proportion of cultured ciliated cells are observed   (MGI Ref ID J:137093)
    • the microtubule ultrastructure of basal bodies and axonemes of mutant renal tubule primary cilia remains normal   (MGI Ref ID J:137093)
  • cellular phenotype
  • abnormal renal tubule epithelial cell primary cilium morphology
    • at 3-4 months of age, the average length of mutant renal tubule primary cilia is significantly increased relative to that in wild-type kidneys   (MGI Ref ID J:137093)
    • in culture, wild-type renal tubule epithelial cells of mostly of collecting duct origin maintain a constant ciliary length between days 7 and 10, whereas mutant cilia display an initial delay but surpass the length of wild-type cilia by 10 days   (MGI Ref ID J:137093)
    • however, no differences in the cellular composition or proportion of cultured ciliated cells are observed   (MGI Ref ID J:137093)
    • the microtubule ultrastructure of basal bodies and axonemes of mutant renal tubule primary cilia remains normal   (MGI Ref ID J:137093)
  • homeostasis/metabolism phenotype
  • decreased salivation
    • no salivation is seen when mutants bite on a dowel   (MGI Ref ID J:94467)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Bbs4tm1Vcs/Bbs4tm1Vcs

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • mortality/aging
  • partial preweaning lethality
    • litters contain fewer than expected homozygous mutants   (MGI Ref ID J:90812)
  • adipose tissue phenotype
  • increased total body fat amount
    • increased weight gain is associated with an increase in centrally deposited adipose tissue   (MGI Ref ID J:90812)
  • behavior/neurological phenotype
  • polyphagia
    • post weaning weight gain is associated with a greater food intake in homozygous mutants compared to wild-type littermates   (MGI Ref ID J:90812)
  • growth/size/body phenotype
  • decreased birth body size
    • homozygous mutants are smaller than wild-type mice at birth   (MGI Ref ID J:90812)
  • decreased body weight
    • at 3 weeks of age homozygous mutants weigh less than their wild-type littermates   (MGI Ref ID J:90812)
  • increased total body fat amount
    • increased weight gain is associated with an increase in centrally deposited adipose tissue   (MGI Ref ID J:90812)
  • obese
    • after weaning homozygous mutants gain more weight and become obese   (MGI Ref ID J:90812)
  • reproductive system phenotype
  • absent sperm flagellum
    • flagella are absent throughout the seminiferous tubules, even on cells with condensed sperm heads   (MGI Ref ID J:90812)
  • male infertility
    • homozygous males fail to sire offspring   (MGI Ref ID J:90812)
  • vision/eye phenotype
  • retinal degeneration
    • progressive retinal degeneration and increased apoptosis are seen by 6 weeks of age   (MGI Ref ID J:90812)
    • by 7 months photoreceptor cells are absent   (MGI Ref ID J:90812)
  • cellular phenotype
  • absent sperm flagellum
    • flagella are absent throughout the seminiferous tubules, even on cells with condensed sperm heads   (MGI Ref ID J:90812)
View Research Applications

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

Developmental Biology Research
Growth Defects
      Growth Defects (homozygous)

Diabetes and Obesity Research
Obesity Without Diabetes

Reproductive Biology Research
Fertility Defects
      males only

Sensorineural Research
Retinal Degeneration

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Bbs4tm1Vcs
Allele Name targeted mutation 1, Val C Sheffield
Allele Type Targeted (Null/Knockout)
Common Name(s) Bbs4-; Bbs4tm1Shef;
Mutation Made By Val Sheffield,   University of Iowa, HHMI
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Bbs4, Bardet-Biedl syndrome 4 (human)
Chromosome 9
Gene Common Name(s) AW537059; AW742241; D9Ertd464e; DNA segment, Chr 9, ERATO Doi 464, expressed; expressed sequence AW537059; expressed sequence AW742241;
Molecular Note Exons 6-11 were replaced with a neo cassette, removing approximately one-third of the coding sequence and resulting in a frameshift. Northern blot indicated lack of transcript in kidneys of mutants. [MGI Ref ID J:90812]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mykytyn K; Mullins RF; Andrews M; Chiang AP; Swiderski RE; Yang B; Braun T; Casavant T; Stone EM; Sheffield VC. 2004. Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc Natl Acad Sci U S A 101(23):8664-9. [PubMed: 15173597]  [MGI Ref ID J:90812]

Additional References

Bbs4tm1Vcs related

Berbari NF; Lewis JS; Bishop GA; Askwith CC; Mykytyn K. 2008. Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc Natl Acad Sci U S A 105(11):4242-6. [PubMed: 18334641]  [MGI Ref ID J:133334]

Berbari NF; Pasek RC; Malarkey EB; Yazdi SM; McNair AD; Lewis WR; Nagy TR; Kesterson RA; Yoder BK. 2013. Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice. Proc Natl Acad Sci U S A 110(19):7796-801. [PubMed: 23599282]  [MGI Ref ID J:197356]

Chamling X; Seo S; Bugge K; Searby C; Guo DF; Drack AV; Rahmouni K; Sheffield VC. 2013. Ectopic expression of human BBS4 can rescue Bardet-Biedl syndrome phenotypes in Bbs4 null mice. PLoS One 8(3):e59101. [PubMed: 23554981]  [MGI Ref ID J:199518]

Davis RE; Swiderski RE; Rahmouni K; Nishimura DY; Mullins RF; Agassandian K; Philp AR; Searby CC; Andrews MP; Thompson S; Berry CJ; Thedens DR; Yang B; Weiss RM; Cassell MD; Stone EM; Sheffield VC. 2007. A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity. Proc Natl Acad Sci U S A 104(49):19422-7. [PubMed: 18032602]  [MGI Ref ID J:128532]

Guo DF; Beyer AM; Yang B; Nishimura DY; Sheffield VC; Rahmouni K. 2011. Inactivation of Bardet-Biedl syndrome genes causes kidney defects. Am J Physiol Renal Physiol 300(2):F574-80. [PubMed: 21106857]  [MGI Ref ID J:168735]

Mokrzan EM; Lewis JS; Mykytyn K. 2007. Differences in renal tubule primary cilia length in a mouse model of Bardet-Biedl syndrome. Nephron Exp Nephrol 106(3):e88-96. [PubMed: 17519557]  [MGI Ref ID J:137093]

Nishimura DY; Fath M; Mullins RF; Searby C; Andrews M; Davis R; Andorf JL; Mykytyn K; Swiderski RE; Yang B; Carmi R; Stone EM; Sheffield VC. 2004. Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc Natl Acad Sci U S A 101(47):16588-93. [PubMed: 15539463]  [MGI Ref ID J:94467]

Rahmouni K; Fath MA; Seo S; Thedens DR; Berry CJ; Weiss R; Nishimura DY; Sheffield VC. 2008. Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome. J Clin Invest 118(4):1458-67. [PubMed: 18317593]  [MGI Ref ID J:135832]

Seo S; Guo DF; Bugge K; Morgan DA; Rahmouni K; Sheffield VC. 2009. Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum Mol Genet 18(7):1323-31. [PubMed: 19150989]  [MGI Ref ID J:146158]

Shah AS; Farmen SL; Moninger TO; Businga TR; Andrews MP; Bugge K; Searby CC; Nishimura D; Brogden KA; Kline JN; Sheffield VC; Welsh MJ. 2008. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc Natl Acad Sci U S A 105(9):3380-5. [PubMed: 18299575]  [MGI Ref ID J:132765]

Swiderski RE; Nishimura DY; Mullins RF; Olvera MA; Ross JL; Huang J; Stone EM; Sheffield VC. 2007. Gene expression analysis of photoreceptor cell loss in bbs4-knockout mice reveals an early stress gene response and photoreceptor cell damage. Invest Ophthalmol Vis Sci 48(7):3329-40. [PubMed: 17591906]  [MGI Ref ID J:123272]

Zhang Q; Seo S; Bugge K; Stone EM; Sheffield VC. 2012. BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes. Hum Mol Genet 21(9):1945-53. [PubMed: 22228099]  [MGI Ref ID J:181886]

Zhang Y; Seo S; Bhattarai S; Bugge K; Searby CC; Zhang Q; Drack AV; Stone EM; Sheffield VC. 2014. BBS mutations modify phenotypic expression of CEP290-related ciliopathies. Hum Mol Genet 23(1):40-51. [PubMed: 23943788]  [MGI Ref ID J:203124]

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 & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Homozygous males are infertile.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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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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