Strain Name:

B6;129S-Tc(HSA21)1TybEmcf/J

Stock Number:

010801

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Availability:

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Use Restrictions Apply, see Terms of Use
These Tc1 mice contain 42Mb (approximately 90%) of a freely segregating human fragment of Chromosome 21 Hsa21 containing 269 genes, including most of the gene orthologues located on mouse Chromosome 10 (Mmu10), Mm16, and Mmu17, which have been found to contribute to human Down Syndrome (DS). These mice may be useful for studying the genes involved in human chromosome aneuploidy and its role in DS.

Description

Strain Information

Former Names B6;129S-Tc(Hsa21)1TybEmcf/J    (Changed: 28-MAR-13 )
Type Mutant Stock; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemHeterozygote x F1         (Female x Male)   15-MAR-11
Specieslaboratory mouse
GenerationN6 (10-JUL-13)
Generation Definitions
 
Donating Investigator Elizabeth MC Fisher,   UCL Institute of Neurology

Description
Mice carrying a human fragment of Chromosome 21 (Hsa21) are viable, fertile, and normal in size, only the female carriers consistently transmits the mutation to the germline. When maintained on a background other than (C57BL/6 X 129S8/SvEv) germline transmission is completely abolished. These Tc1 mice contain 42Mb (approximately 83%) of a freely segregating Hsa21 containing 269 genes, including most of the gene orthologues located on mouse Chromosome 10 (Mmu10), Mm16, and Mmu17, which have been found to contribute to human Down Syndrome (DS). This mouse strain represents the most complete model of DS, exhibiting alterations in behavior, learning, memory, synaptic plasticity, cerebellar neuronal number, heart development, mandible size, defects in motor coordination, perturbed haematopoiesis, and reduced tumour angiogenesis. These mice may be useful for studying the genes involved in human chromosome aneuploidy and its role in DS.

Development
This transchromosomal mouse contains a freely segregating human fragment of Chromosome 21 (Hsa21). More specifically, the entire Hsa21 was introduced to female 129S2/SvPas-derived MPI-VI embryonic stem (ES) cells via irradiation microcell-mediated chromosome transfer (XMMCT). Cell line 91-1, which contained 42Mb (approximately 90%) of Hsa21, was injected into blastocysts, and the resulting chimeric females were bred to C57BL/6J males for germline transmission. Offspring that were bred to (C57BL/6J x 129S8)F1 mice retained stable transmission of Hsa21 and were used to establish a colony of Tc1 mice. Upon arrival at The Jackson Laboratory, Tc1 females mice were bred to (C57BL/6J x 129S8/SvEv)F1 males (see Stock No. 000664 and Stock No. 012809) for at least one generation to establish the colony. Tc1 females were subsequently bred to (C57BL/6J x 129S8/SvEv)F1 males to maintain the live colony.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

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

Tc(HSA21)1TybEmcf/0

        involves: 129S2/SvPas * 129S8/SvEv * C57BL/6J
  • cardiovascular system phenotype
  • atrioventricular septal defect
    • one mouse exhibited an atrioventricular septal defect associated with unfused atrioventricular cushions   (MGI Ref ID J:101383)
  • dextrocardia
    • some mice exhibit hearts that are tilted onto their right unlike in wild-type mice   (MGI Ref ID J:101383)
  • failure of atrioventricular cushion closure
    • seen in mice with a full atrioventricular canal defect   (MGI Ref ID J:101383)
  • overriding aortic valve
    • in one mouse that also displayed a ventricular septum defect   (MGI Ref ID J:101383)
  • perimembraneous ventricular septal defect
    • 7 of 11 mice exhibit a perimembranous ventral septal defect such that the ventricular septum fails to fuse to the proximal outflow cushion tracts   (MGI Ref ID J:101383)
  • nervous system phenotype
  • decreased neuron number
    • mice exhibit a reduction in the number of granule neurons in the cerebellum compared to wild-type mice   (MGI Ref ID J:101383)
  • reduced long term potentiation   (MGI Ref ID J:101383)
  • behavior/neurological phenotype
  • abnormal response to novel object
    • mice spend less time exploring a novel object than wild-type mice   (MGI Ref ID J:101383)
  • craniofacial phenotype
  • abnormal mandible morphology
    • mutant mice exhibit a mandible that is smaller between the coronoid process and the mandibular angle and between the coronoid process and the most superior point of the incisor alveolar rim   (MGI Ref ID J:101383)
  • skeleton phenotype
  • abnormal mandible morphology
    • mutant mice exhibit a mandible that is smaller between the coronoid process and the mandibular angle and between the coronoid process and the most superior point of the incisor alveolar rim   (MGI Ref ID J:101383)

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

Tc(HSA21)1TybEmcf/0

        involves: 129P2/OlaHsd * BALB/c * C3H/HeH * C57BL/6
  • behavior/neurological phenotype
  • abnormal learning/memory/conditioning   (MGI Ref ID J:167359)
    • abnormal spatial learning
      • slower to learn task in a Morris Maze test   (MGI Ref ID J:167359)
      • travelled further to find the hidden platform   (MGI Ref ID J:167359)
    • abnormal spatial reference memory
      • little retention of learning seen during probe trials in a Morris Maze test   (MGI Ref ID J:167359)
  • abnormal motor coordination/ balance   (MGI Ref ID J:167359)
    • impaired coordination
      • perform poorly on a rotarod   (MGI Ref ID J:167359)
      • fall of a rotarod more rapidly and at slower speeds   (MGI Ref ID J:167359)
      • rotarod performance does not improve with practice   (MGI Ref ID J:167359)
    • impaired limb coordination
      • 25% more errors than controls on a notched bar test of hindlimb performance   (MGI Ref ID J:167359)
  • abnormal social investigation
    • no distinction made between mice after the later introduction of a second new mouse   (MGI Ref ID J:167359)
    • investigation of a newly introduced mouse is normal   (MGI Ref ID J:167359)
  • decreased anxiety-related response
    • less time spent in the periphery of an open field test   (MGI Ref ID J:167359)
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      heart

Neurobiology Research
Down syndrome

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tc(HSA21)1TybEmcf
Allele Name transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher
Allele Type Not Applicable
Common Name(s) Tc(HSA21)91-1Emcf; Tc1;
Strain of Origin129S2/SvPas
Gene Symbol and Name Tc(HSA21)1TybEmcf, transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher
Chromosome UN
Gene Common Name(s) Tc(HSA21)91-1Emcf; transchromosomal, human 21, line 91-1 Elizabeth M C Fisher;
General Note ES cell line = MPI-VI.
Molecular Note A freely segregating chromosome composed of 42 Mb, or 90%, of human chromosome 21 (spanning D21S5-CXADR, D21S1922-IFNAR1 and RUNX1-COL6A1) was created in MPI-VI (129S2/SvPas) ES cells using irradiated microcell-mediated chromosome transfer. [MGI Ref ID J:101383]

Genotyping

Genotyping Information

Genotyping Protocols

Tc(Hsa21)1TybEmcf, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

O'Doherty A; Ruf S; Mulligan C; Hildreth V; Errington ML; Cooke S; Sesay A; Modino S; Vanes L; Hernandez D; Linehan JM; Sharpe PT; Brandner S; Bliss TV; Henderson DJ; Nizetic D; Tybulewicz VL; Fisher EM. 2005. An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309(5743):2033-7. [PubMed: 16179473]  [MGI Ref ID J:101383]

Additional References

Tc(HSA21)1TybEmcf related

Ahmed MM; Dhanasekaran AR; Tong S; Wiseman FK; Fisher EM; Tybulewicz VL; Gardiner KJ. 2013. Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain. Hum Mol Genet 22(9):1709-24. [PubMed: 23349361]  [MGI Ref ID J:194982]

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]

Canzonetta C; Mulligan C; Deutsch S; Ruf S; O'Doherty A; Lyle R; Borel C; Lin-Marq N; Delom F; Groet J; Schnappauf F; De Vita S; Averill S; Priestley JV; Martin JE; Shipley J; Denyer G; Epstein CJ; Fillat C; Estivill X; Tybulewicz VL; Fisher EM; Antonarakis SE; Nizetic D. 2008. DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome. Am J Hum Genet 83(3):388-400. [PubMed: 18771760]  [MGI Ref ID J:140118]

Duchon A; Pothion S; Brault V; Sharp AJ; Tybulewicz VL; Fisher EM; Herault Y. 2011. The telomeric part of the human chromosome 21 from Cstb to Prmt2 is not necessary for the locomotor and short-term memory deficits observed in the Tc1 mouse model of Down syndrome. Behav Brain Res 217(2):271-81. [PubMed: 21047530]  [MGI Ref ID J:167359]

Galante M; Jani H; Vanes L; Daniel H; Fisher EM; Tybulewicz VL; Bliss TV; Morice E. 2009. Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome. Hum Mol Genet 18(8):1449-63. [PubMed: 19181682]  [MGI Ref ID J:146862]

Gribble SM; Wiseman FK; Clayton S; Prigmore E; Langley E; Yang F; Maguire S; Fu B; Rajan D; Sheppard O; Scott C; Hauser H; Stephens PJ; Stebbings LA; Ng BL; Fitzgerald T; Quail MA; Banerjee R; Rothkamm K; Tybulewicz VL; Fisher EM; Carter NP. 2013. Massively parallel sequencing reveals the complex structure of an irradiated human chromosome on a mouse background in the Tc1 model of Down syndrome. PLoS One 8(4):e60482. [PubMed: 23596509]  [MGI Ref ID J:200117]

Grizenkova J; Akhtar S; Hummerich H; Tomlinson A; Asante EA; Wenborn A; Fizet J; Poulter M; Wiseman FK; Fisher EM; Tybulewicz VL; Brandner S; Collinge J; Lloyd SE. 2012. Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice. Proc Natl Acad Sci U S A 109(34):13722-7. [PubMed: 22869728]  [MGI Ref ID J:188604]

Haas MA; Bell D; Slender A; Lana-Elola E; Watson-Scales S; Fisher EM; Tybulewicz VL; Guillemot F. 2013. Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome. PLoS One 8(10):e78561. [PubMed: 24205261]  [MGI Ref ID J:209227]

Mahadevaiah SK; Bourc'his D; de Rooij DG; Bestor TH; Turner JM; Burgoyne PS. 2008. Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182(2):263-76. [PubMed: 18663141]  [MGI Ref ID J:139518]

Pope BD; Chandra T; Buckley Q; Hoare M; Ryba T; Wiseman FK; Kuta A; Wilson MD; Odom DT; Gilbert DM. 2012. Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse. Hum Mol Genet 21(19):4162-70. [PubMed: 22736031]  [MGI Ref ID J:187410]

Reynolds LE; Watson AR; Baker M; Jones TA; D'Amico G; Robinson SD; Joffre C; Garrido-Urbani S; Rodriguez-Manzaneque JC; Martino-Echarri E; Aurrand-Lions M; Sheer D; Dagna-Bricarelli F; Nizetic D; McCabe CJ; Turnell AS; Kermorgant S; Imhof BA; Adams R; Fisher EM; Tybulewicz VL; Hart IR; Hodivala-Dilke KM. 2010. Tumour angiogenesis is reduced in the Tc1 mouse model of Down's syndrome. Nature 465(7299):813-7. [PubMed: 20535211]  [MGI Ref ID J:161946]

Sheppard O; Plattner F; Rubin A; Slender A; Linehan JM; Brandner S; Tybulewicz VL; Fisher EM; Wiseman FK. 2012. Altered regulation of tau phosphorylation in a mouse model of down syndrome aging. Neurobiol Aging 33(4):828.e31-44. [PubMed: 21843906]  [MGI Ref ID J:188193]

Spellman C; Ahmed MM; Dubach D; Gardiner KJ. 2013. Expression of trisomic proteins in Down syndrome model systems. Gene 512(2):219-25. [PubMed: 23103828]  [MGI Ref ID J:192164]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, Tc1 females are bred to (C57BL/6J x 129S8/SvEv)F1 males (see Stock No. 000664 and Stock No. 012809) to maintain the live colony. Tc1 males do not consistently transmit mutation to germline, and transmission is completely lost on some congenic backgrounds.
Mating SystemHeterozygote x F1         (Female x Male)   15-MAR-11
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 $239.00Female or MaleHeterozygous for Tc(HSA21)1TybEmcf  
Price per Pair (US dollars $)Pair Genotype
$374.00Heterozygous for Tc(HSA21)1TybEmcf x B6129S8F1/J (012868)  

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 $310.70Female or MaleHeterozygous for Tc(HSA21)1TybEmcf  
Price per Pair (US dollars $)Pair Genotype
$486.20Heterozygous for Tc(HSA21)1TybEmcf x B6129S8F1/J (012868)  

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
   Wild-type from the colony
 
  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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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