Overview

Also Known As: Tc1, Tc(HSA21)91-1Emcf

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 orthologs located on mouse Chromosome 10 (Mmu10), Mmu16, 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.

Donating Investigator

Elizabeth MC Fisher, UCL Institute of Neurology

Genetic overview

Genetic Background	Generation

Tc(HSA21)1TybEmcf

Allele Type	Gene Symbol	Gene Name
Not Applicable (Inserted expressed sequence, Humanized sequence)	Tc(HSA21)1TybEmcf	transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher

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Research Applications

Neurobiology Research
Developmental Biology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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 orthologs located on mouse Chromosome 10 (Mmu10), Mmu16, 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 hematopoiesis, and reduced tumor 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 B6129S8F1/J males (Stock No. 012868) males for at least one generation to establish the colony. Tc1 females were subsequently bred to B6129S8F1/J males to maintain the live colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

B6129S8F1/J (Stock No. 012868) may be an appropriate control.

Additional Information

Considerations for Choosing Controls

Selected References

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):2033-7PubMed: 16179473 MGI: J:101383

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Genetics

Tc(HSA21)1TybEmcf

Allele Symbol: Tc(HSA21)1TybEmcf

Allele Name	transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher
Allele Type	Not Applicable (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher; Tc(HSA21)1TybEmcf
Gene Symbol and Name	Tc(HSA21)1TybEmcf, transchromosomal, human 21, line 1, Victor Tybulewicz and Elizabeth M C Fisher
Gene Synonym(s)	Tc(HSA21)91-1Emcf; Tc(HSA21)91-1Emcf; transchromosomal, human 21, line 91-1 Elizabeth M C Fisher
Strain of Origin	129S2/SvPas
Chromosome	UN
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.

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Down syndrome

Research Areas By Genotype

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

Neurobiology Research
- Down syndrome
Developmental Biology Research
- Internal/Organ Defects
  - heart
Mouse/Human Gene Homologs
- Down syndrome

Mammalian Phenotype Terms by Genotype

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

Genotype: Tc(HSA21)1TybEmcf/0
involves: 129P2/OlaHsd * BALB/c * C3H/HeH * C57BL/6

behavior/neurological phenotype

abnormal learning/memory/conditioning

abnormal motor coordination/balance

abnormal social investigation
- Normal - investigation of a newly introduced mouse is normal
- no distinction made between mice after the later introduction of a second new mouse

abnormal spatial learning
- slower to learn task in a Morris Maze test
- travelled further to find the hidden platform

abnormal spatial reference memory
- little retention of learning seen during probe trials in a Morris Maze test

decreased anxiety-related response
- less time spent in the periphery of an open field test

impaired coordination
- fall of a rotarod more rapidly and at slower speeds
- perform poorly on a rotarod
- rotarod performance does not improve with practice

impaired limb coordination
- 25% more errors than controls on a notched bar test of hindlimb performance

The following phenotype relates to a compound genotype created using this strain

Genotype: Tc(HSA21)1TybEmcf/0
involves: 129S2/SvPas * 129S8/SvEv * C57BL/6J

behavior/neurological phenotype

abnormal response to novel object
- mice spend less time exploring a novel object than wild-type mice

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

cardiovascular system phenotype

atrioventricular septal defect
- one mouse exhibited an atrioventricular septal defect associated with unfused atrioventricular cushions

dextrocardia
- some mice exhibit hearts that are tilted onto their right unlike in wild-type mice

failure of atrioventricular cushion closure
- seen in mice with a full atrioventricular canal defect

overriding aortic valve
- in one mouse that also displayed a ventricular septum defect

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

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

nervous system phenotype

decreased neuron number
- mice exhibit a reduction in the number of granule neurons in the cerebellum compared to wild-type mice

reduced long term potentiation

References

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):2033-7PubMed: 16179473 MGI: J:101383

Additional - Tc(HSA21)1TybEmcf related

Technical Support

Contact Technical Support

Genotyping Protocols
- High Resolution Melting: Tc(Hsa21)1TybEmcf
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, Tc1 females are bred to B6129S8F1/J males (Stock No. 012868) to maintain the live colony. Tc1 males do not consistently transmit mutation to germline, and transmission is completely lost on some congenic backgrounds.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x F1
Citation
When using the Tc1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #010801 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

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Commercial & For-Profit

Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildtype for Tc(HSA21)1TybEmcf

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

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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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Licensing Information

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Also Known As: Tc1, Tc(HSA21)91-1Emcf

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tc(HSA21)1TybEmcf

Allele Symbol: Tc(HSA21)1TybEmcf

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tc(HSA21)1TybEmcf/0involves: 129P2/OlaHsd * BALB/c * C3H/HeH * C57BL/6

behavior/neurological phenotype

Genotype: Tc(HSA21)1TybEmcf/0involves: 129S2/SvPas * 129S8/SvEv * C57BL/6J

behavior/neurological phenotype

skeleton phenotype

cardiovascular system phenotype

craniofacial phenotype

nervous system phenotype

References

Additional - Tc(HSA21)1TybEmcf related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tc(HSA21)1TybEmcf/0
involves: 129P2/OlaHsd * BALB/c * C3H/HeH * C57BL/6

Genotype: Tc(HSA21)1TybEmcf/0
involves: 129S2/SvPas * 129S8/SvEv * C57BL/6J