Overview

These DYRK1A transgenic mice represent a clinically relevant animal model for a variety of Down Syndrome features including mental retardation, Alzheimer's Disease-like brain pathology, and increased food intake.

Donating Investigator

Woojoo Song, Inje University

Woo-joo Song, Kyung Hee University School of Medicine

Genetic overview

Genetic Background	Generation

Tg(DYRK1A)36Wjs

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Neurobiology Research
Internal/Organ Research
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a) gene is located in the "Down Syndrome critical region" of human chromosome 21. It is ubiquitously expressed in both fetal and adult tissues of humans and rodents, with strongest expression in the heart and brain. Expression of DYRK1A protein is increased in the brains of human patients with Down Syndrome and Alzheimer's Disease. Interacting with a number of biological pathways, the full function of this gene is still being elucidated.

These hemizygous mice carry a single copy of a bacterial artificial chromosome (BAC) clone that contains the complete human DYRK1A genomic fragment, including the endogenous promoter. No other genes are included in the BAC. Protein expression is elevated 1.5-2 fold.

Hemizygotes show a significant impairment in hippocampal-dependent memory tasks as well as alterations in two forms of synaptic plasticity. Proliferation of embryonic neuronal cells is inhibited.

Many Down Syndrome patients show an early onset of Alzheimer's Disease and these mice demonstrate that DYRK1A hyperphosphorylates Tau at residues Ser-202, Thr-212, and Ser-404. DYRK1A also phosphorylates APP (amyloid beta (A4) precursor protein), RCAN1 (regulator of calcineurin 1), and PSEN1 (presenilin 1).

Transgenic mice exhibit significantly reduced bone mass despite decreased osteoclastogenesis. This is reminiscent of the osteoporotic bone phenotype in Down Syndrome patients.

Pathways that regulate food intake are also affected by DYRK1A. These transgenic animals demonstrate increase food intake through the Sir2-FOXO-sNPF/NPY pathway.

These transgenic mice represent a clinically relevant animal model for a variety of Down Syndrome features including mental retardation, Alzheimer's Disease-like brain pathology, and increased food intake. Hemizygotes show normal viability and fertility.

Development

A linearized BAC (clone 777J19 from the RPCI-11 library) encoding only full-length human DYRK1A (including the promoter) was injected into C57BL/6NCrjBgi embryos. A single copy was integrated in the mouse genome. This strain was backcrossed to C57BL/6J by the donating laboratory.

Expression Data

Expressed Gene	DYRK1A, dual specificity tyrosine phosphorylation regulated kinase 1A, human
Site of Expression

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Ahn KJ; Jeong HK; Choi HS; Ryoo SR; Kim YJ; Goo JS; Choi SY; Han JS; Ha I; Song WJ. 2006. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 22(3):463-72PubMed: 16455265 MGI: J:111293

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Genetics

Tg(DYRK1A)36Wjs

Allele Symbol: Tg(DYRK1A)36Wjs

Allele Name	transgene insertion 36, Woo-Joo Song
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Tg(DYRK1A)36Wjs; transgene insertion 36, Woo-Joo Song
Gene Symbol and Name	Tg(DYRK1A)36Wjs, transgene insertion 36, Woo-Joo Song
Gene Synonym(s)	DYRK1A BAC TG
Promoter	DYRK1A, dual specificity tyrosine phosphorylation regulated kinase 1A, human
Expressed Gene	DYRK1A, dual specificity tyrosine phosphorylation regulated kinase 1A, human
Strain of Origin	C57BL/6NCrjBgi
Chromosome	UN
Molecular Note	This transgene consists of a bacterial artificial chromosome clone containing the complete human DYRK1A genomic DNA fragment, including the endogenous promoter (777J19 BAC clone from the RPCI-11 human BAC library). FISH and quantitative PCR analysis shows a single chromosomal integration of the DNA and about a 1.5-fold overexpression of total Dyrk1a (both mouse and human) protein. Two lines 36 and 46 were created, with line 36 entered as the representative line.
Mutations Made By	Woo-joo Song, Kyung Hee University School of Medicine

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
- Neurodevelopmental Defects
- Behavioral and Learning Defects
- Down syndrome
- Alzheimer's Disease
Internal/Organ Research
- Skeleton
  - Bone
Cell Biology Research
- Signal Transduction

Mammalian Phenotype Terms by Genotype

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

Genotype: Tg(DYRK1A)36Wjs/0
involves: C57BL/6NCrjBgi

behavior/neurological phenotype

abnormal motor coordination/balance
- Normal - however, no other motor abnormalities are apparent
- mutants show a slight delay in balancing during rotarod training at the first trial but they maintain their balance in subsequent training sessions

abnormal spatial reference memory
- in probe trials, where the platform was removed after the 4th, 6th, and 8th day of training, mutants do not show any improvement with training, indicating that mice do not learn the location of the platform
- in the Morris water maze with hidden platform, mutants do not show any improvement in finding the hidden platform during training, even after repeated training for 8 days, indicating severe spatial memory impairment

cellular phenotype

abnormal neuron proliferation
- embryonic neocortical neuronal cells at E14.5 exhibit impaired proliferation

abnormal neuronal precursor proliferation
- primary cortical neural stem cell precursors from E12.5 embryos exhibit impaired proliferation

nervous system phenotype

abnormal long term depression
- magnitude of the LTD measured for 65 minutes after conditioning is higher than in controls

abnormal neuron proliferation
- embryonic neocortical neuronal cells at E14.5 exhibit impaired proliferation

abnormal neuronal precursor proliferation
- primary cortical neural stem cell precursors from E12.5 embryos exhibit impaired proliferation

enhanced long term potentiation
- stimulation at an intermediate frequency of 900 pulses at 10 Hz produces a modest enhancement of potentiation compared to controls
- theta-burst stimulation at 100 Hz yields a greater increase in LTP than in controls

impaired synaptic plasticity
- altered bidirectional synaptic plasticity, with a shift in plasticity toward a greater induction of long term potentiation (LTP) and a lesser induction of long term depression (LTD)
- Normal - basal synaptic transmission is normal

increased brain weight
- 19% increase in brain weight at 9 weeks of age, however body weights were no different from controls

reduced long term depression
- LTD at paired-pulse low frequency stimulation is reduced in hippocampal slices

References

Ahn KJ; Jeong HK; Choi HS; Ryoo SR; Kim YJ; Goo JS; Choi SY; Han JS; Ha I; Song WJ. 2006. DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 22(3):463-72PubMed: 16455265 MGI: J:111293

Additional - Tg(DYRK1A)36Wjs related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Tg(DYRK1A)36Wjs
- Genotyping resources and troubleshooting
Breeding Considerations

Hemizygotes are viable and fertile. The single transgenic copy, in addition to the two endogenous mouse genes, creates a trisomic model of Down Syndrome.
- Additional Breeding and Husbandry Support
Citation
When using the C57BL/6-Tg(DYRK1A)36Wjs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019460 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

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(DYRK1A)36Wjs

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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(DYRK1A)36Wjs

Allele Symbol: Tg(DYRK1A)36Wjs

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: Tg(DYRK1A)36Wjs/0involves: C57BL/6NCrjBgi

behavior/neurological phenotype

cellular phenotype

nervous system phenotype

References

Additional - Tg(DYRK1A)36Wjs related

Genotyping Protocols

Breeding Considerations

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

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: Tg(DYRK1A)36Wjs/0
involves: C57BL/6NCrjBgi