Strain Name:

B6.129S6-Dp(16Cbr1-ORF9)1Rhr/J

Stock Number:

005383

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Availability:

Cryopreserved - Ready for recovery

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Common Names: Ts1Rhr;    

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 B6.129S6-Is(16Cbr1-ORF9)1Rhr/J    (Changed: 08-APR-05 )
B6.129S6-Is(16Cbr1-ORF9)1Rhr    (Changed: 07-APR-05 )
Type Chromosome Aberration; Duplication; Insertion;
Additional information on Mice with Chromosomal Aberrations.
Type Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?+N1p (09-NOV-05)
Generation Definitions
 
Donating Investigator Roger H. Reeves,   Johns Hopkins Univ. Schl. Med

Description
These mice are trisomic for the mouse chromosome segment orthologus to the human chromosome 21 Down syndrome critical region (DSCR). The borders of the 3.9 Mb region are defined by the carbonyl reductase 1 gene and a site adjacent to the myxovirus (influenza virus) resistance 2 locus. Trisomic mice are viable, fertile and are significantly larger than euploid littermates. Mandible size is enlarged as is skull size, with an overall elongation of the rostrocaudal aspect in comparison to euploid littermates. This mouse may be useful in studies exploring the consequences of polyploidy involving the DSCR.

Development
A targeting vector was used to introduce a sequence encoding a 3'portion of a neomycin resistance gene, a loxP site and a hygromycin resistance gene at the carbonyl reductase 1 locus in 129S6/SvEv-derived MC1 embryonic stem (ES) cells. Correctly targeted ES cells were selected and electroporated with another targeting vector designed to orient a puromycin resistance gene, a loxP site and a 5'portion of a neomycin resistance gene, adjacent to the myxovirus (influenza virus) resistance 2 locus. A CAGGS-cre expression vector was electroporated into ES cells harboring both targeted mutations. Cre-mediated recombinants that possessed a functional neomycin resistance gene were obtained and injected into ICR blastocysts. Chimeric animals were crossed to C57BL/6 mice for at least 8 generations (4/2005).

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Duplication
005536   B6.129S7-Dp(11Cops3-Rnf112)1Jrl/J
View Duplication     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Down Syndrome
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Dp(16Cbr1-ORF9)1Rhr/0

        B6.129S6-Dp(16Cbr1-ORF9)1Rhr
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mice perform similar to control mice in a Morris water maze with a visible or hidden platform and have normal long term potentials   (MGI Ref ID J:121764)

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

Dp(16Cbr1-ORF9)1Rhr/0

        involves: 129S6/SvEvTac * C57BL/6
  • nervous system phenotype
  • decreased brain size
    • brain size is 85% of that in control mice   (MGI Ref ID J:121764)
  • small cerebellum
    • cerebellum size if 95% of that in control mice   (MGI Ref ID J:121764)
  • growth/size/body phenotype
  • increased body size   (MGI Ref ID J:93223)
    • increased body weight   (MGI Ref ID J:121764)
  • skeleton phenotype
  • abnormal mandible morphology
    • mandibles are overall enlarged   (MGI Ref ID J:93223)
  • enlarged cranium   (MGI Ref ID J:93223)
  • long femur   (MGI Ref ID J:93223)
  • craniofacial phenotype
  • abnormal mandible morphology
    • mandibles are overall enlarged   (MGI Ref ID J:93223)
  • enlarged cranium   (MGI Ref ID J:93223)
  • limbs/digits/tail phenotype
  • long femur   (MGI Ref ID J:93223)

Dp(16Cbr1-ORF9)1Rhr/0

        involves: 129S6/SvEvTac * C3H/HeSnJ * C57BL/6Ei
  • nervous system phenotype
  • abnormal dendrite morphology
    • dendritic spine density in the fascia dentate is decreased 14% compared to in wild-type mice   (MGI Ref ID J:148478)
    • the area of spine head in the fascia dentata is increased compared to in wild-type mice   (MGI Ref ID J:148478)
    • however, the length of spine necks in the fascia dentate is normal   (MGI Ref ID J:148478)
    • the average width of dendrites in layers II to III apical oblique is decreased compared to in wild-type mice   (MGI Ref ID J:148478)
    • the area of spine head in layers II to III is increased compared to in wild-type mice   (MGI Ref ID J:148478)
  • enlarged hippocampus
    • the hippocampus volume is enlarged compared to in wild-type mice   (MGI Ref ID J:148478)
  • increased brain weight
    • at 7.5 months   (MGI Ref ID J:148478)
  • reduced long term potentiation
    • tetanization protocols fail to induce long term potentiation (LTP) unlike in wild-type mice   (MGI Ref ID J:148478)
    • however, treatment with picrotoxin restores the ability of tetanization to induce LTP   (MGI Ref ID J:148478)
  • thickened cerebral cortex
    • the motor cortex thicker than in wild-type mice   (MGI Ref ID J:148478)
  • behavior/neurological phenotype
  • abnormal object recognition memory
    • mice exhibit impaired object recognition compared with wild-type mice   (MGI Ref ID J:148478)
  • abnormal response to novel object
    • mice exhibit a lack of interest towards a novel object compared with wild-type mice   (MGI Ref ID J:148478)
  • abnormal spatial working memory
    • mice exhibit inferior performance in a T-maze compared with wild-type mice   (MGI Ref ID J:148478)
  • decreased vertical activity
    • during the light cycle, mice spend less time rearing than wild-type mice   (MGI Ref ID J:148478)
    • however, other locomotor activities are normal during the light cycle   (MGI Ref ID J:148478)
  • increased thigmotaxis
    • mice spend more time and travel a longer distance in the periphery of an open field compared with wild-type mice   (MGI Ref ID J:148478)
  • growth/size/body phenotype
  • increased body weight
    • at 3 and 3.5 months   (MGI Ref ID J:148478)

Dp(16Cbr1-ORF9)1Rhr/0

        involves: 129S6/SvEvTac
  • hematopoietic system phenotype
  • abnormal common myeloid progenitor cell morphology
    • mutants have an altered proportion of myeloid progenitors, characterized by a shift from megakaryocyte-erythroid progenitors toward granulocyte-monocyte progenitors and an increased proportion of CFU-GM colonies   (MGI Ref ID J:184564)
  • abnormal megakaryocyte progenitor cell morphology
    • bone marrow and spleen cells show an increased ability to form CFU-megakaryocyte colonies in vitro, but not erythroid BFU-Es   (MGI Ref ID J:184564)
    • increased megakaryocyte cell number   (MGI Ref ID J:184564)
    • increased platelet cell number
      • mutants develop a progressive myeloproliferative disorder associated with thrombocytosis   (MGI Ref ID J:184564)
  • decreased erythrocyte cell number
    • mutants have reduced red blood cell counts   (MGI Ref ID J:184564)
  • increased hematopoietic stem cell number
    • E13.5 embryos show an increase of reconstituting fetal hematopoietic stem cells   (MGI Ref ID J:184564)
  • tumorigenesis
  • *normal* tumorigenesis
    • mutants do not develop leukemia   (MGI Ref ID J:184564)
View Research Applications

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

Dp(16Cbr1-ORF9)1Rhr related

Neurobiology Research
Down syndrome

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dp(16Cbr1-ORF9)1Rhr
Allele Name duplication, Chr 16, H R Reeves 1
Allele Type Targeted
Common Name(s) Ts1Rhr;
Mutation Made By Roger Reeves,   Johns Hopkins Univ. Schl. Med
Strain of Origin129S6/SvEvTac
ES Cell Line NameMC1
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Dp(16Cbr1-ORF9)1Rhr, duplication, Chr 16, H R Reeves 1
Chromosome 16
Gene Common Name(s) Is(16Cbr1-ORF9)1Rhr; Is(16Mx2-Cbr1)1Rhr; Is(16Mx2-Cbrl)1Rhr; Ts(1616)1Rhr; insertion, Chr 16, H R Reeves 1; trisomy, Chr 16 translocation to Chr 16, H R Reeves 1;
Molecular Note A duplication of a 3.9 Mb region on chromosome 16 was engineered by Cre-mediated recombination between inserted loxP sites located on different chromosomes. This duplicated segment contains mouse orthologs of 33 conserved and minimally conserved genes in the human Down syndrome critical region. [MGI Ref ID J:93223]

Genotyping

Genotyping Information

Genotyping Protocols

Dp(16Cbr1-ORF9)1Rhr, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Olson LE; Richtsmeier JT; Leszl J; Reeves RH. 2004. A chromosome 21 critical region does not cause specific down syndrome phenotypes. Science 306(5696):687-90. [PubMed: 15499018]  [MGI Ref ID J:93223]

Additional References

Dp(16Cbr1-ORF9)1Rhr related

Belichenko NP; Belichenko PV; Kleschevnikov AM; Salehi A; Reeves RH; Mobley WC. 2009. The 'Down syndrome critical region' is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome. J Neurosci 29(18):5938-48. [PubMed: 19420260]  [MGI Ref ID J:148478]

Belichenko PV; Masliah E; Kleschevnikov AM; Villar AJ; Epstein CJ; Salehi A; Mobley WC. 2004. Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome. J Comp Neurol 480(3):281-98. [PubMed: 15515178]  [MGI Ref ID J:94569]

Bhutta MF; Cheeseman MT; Herault Y; Yu YE; Brown SD. 2013. Surveying the Down syndrome mouse model resource identifies critical regions responsible for chronic otitis media. Mamm Genome :. [PubMed: 24068166]  [MGI Ref ID J:201811]

Blank M; Fuerst PG; Stevens B; Nouri N; Kirkby L; Warrier D; Barres BA; Feller MB; Huberman AD; Burgess RW; Garner CC. 2011. The Down Syndrome Critical Region Regulates Retinogeniculate Refinement. J Neurosci 31(15):5764-5776. [PubMed: 21490218]  [MGI Ref ID J:170968]

Deitz SL; Roper RJ. 2011. Trisomic and allelic differences influence phenotypic variability during development of down syndrome mice. Genetics 189(4):1487-95. [PubMed: 21926299]  [MGI Ref ID J:178735]

Dunlevy L; Bennett M; Slender A; Lana-Elola E; Tybulewicz VL; Fisher EM; Mohun T. 2010. Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse. Cardiovasc Res 88(2):287-95. [PubMed: 20558441]  [MGI Ref ID J:182114]

Malinge S; Bliss-Moreau M; Kirsammer G; Diebold L; Chlon T; Gurbuxani S; Crispino JD. 2012. Increased dosage of the chromosome 21 ortholog Dyrk1a promotes megakaryoblastic leukemia in a murine model of Down syndrome. J Clin Invest 122(3):948-62. [PubMed: 22354171]  [MGI Ref ID J:184564]

Olson LE; Roper RJ; Sengstaken CL; Peterson EA; Aquino V; Galdzicki Z; Siarey R; Pletnikov M; Moran TH; Reeves RH. 2007. Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet 16(7):774-82. [PubMed: 17339268]  [MGI Ref ID J:121764]

Rachidi M; Lopes C. 2007. Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms. Neurosci Res 59(4):349-69. [PubMed: 17897742]  [MGI Ref ID J:128743]

Sussan TE; Yang A; Li F; Ostrowski MC; Reeves RH. 2008. Trisomy represses Apc(Min)-mediated tumours in mouse models of Down's syndrome. Nature 451(7174):73-5. [PubMed: 18172498]  [MGI Ref ID J:131046]

Wiseman FK; Alford KA; Tybulewicz VL; Fisher EM. 2009. Down syndrome--recent progress and future prospects. Hum Mol Genet 18(R1):R75-83. [PubMed: 19297404]  [MGI Ref ID J:156661]

Zhang L; Fu D; Belichenko PV; Liu C; Kleschevnikov AM; Pao A; Liang P; Clapcote SJ; Mobley WC; Yu YE. 2012. Genetic analysis of Down syndrome facilitated by mouse chromosome engineering. Bioeng Bugs 3(1):8-12. [PubMed: 22126738]  [MGI Ref ID J:196862]

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 maintaining a live colony, these mice are maintained in a trisomic state by crossing to wildtype C57BL/6J mice.
Diet Information LabDiet® 5K52/5K67

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 willfulfill 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 willfulfill 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.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (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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