Strain Name:

B6N.Cg-Tg(Prnp-TARDBP*Q331K)103Dwc/J

Stock Number:

017933

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Availability:

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Prp-TDP-43Q331K [~1.5x] transgenic mice have expression of a myc-tagged, human TAR DNA binding protein carrying the ALS-linked Q331K mutation (huTDP-43*Q331K) directed to brain and spinal cord by the mouse prion protein promoter. Along with the lower huTDP-43*Q331K expressing founder line (Prp-TDP-43Q331K-low; Stock No. 017930), these Prp-TDP-43Q331K [~1.5x] transgenic mice may be useful in studying motor dysfunction in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease), specifically motor dysfunction and L5 motor axon/lower motor neuron degeneration.

Description

Strain Information

Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemNoncarrier x Hemizygote         (Female x Male)   01-OCT-12
Mating SystemHemizygote x Noncarrier         (Female x Male)   01-OCT-12
Specieslaboratory mouse
GenerationN9pN1+N1F3 (06-AUG-14)
Generation Definitions
 
Donating InvestigatorDr. Don Cleveland,   Ludwig Institute for Cancer Res. (UCSD)

Description
Prp-TDP-43Q331K transgenic mice express a myc-tagged, human TAR DNA binding protein cDNA sequence modified to have the ALS-linked Q331K mutation (huTDP-43*Q331K), all under the direction of the mouse prion protein promoter (PrP). As expected for the PrP promoter, transgene expression is confined primarily to central nervous system (brain and spinal cord), with very low to no expression in other tested tissues (testis not examined). Anti-myc antibody staining shows huTDP-43*Q331K accumulation in the nuclei of neurons as well as glial cells of the spinal cord and brain, with a corresponding downregulation of endogenous mouse TDP-43. The transgene is flanked by loxP sites, allowing it to be removed by introduction of Cre recombinase if desired. The phenotype below describes Prp-TDP-43Q331K transgenic mice from founder line 103 (Prp-TDP-43Q331K [~1.5x]).
The Prp-TDP-43Q331K [~1.5x] mice have moderate overexpression levels in total TDP-43 mRNA/protein, with an ~2.5-fold increase in total TDP-43 expression (huTDP-43*Q331K levels ~1.5-fold greater) compared to endogenous TDP-43 in non-transgenic mice. By three months of age, Prp-TDP-43Q331K [~1.5x] mice develop adult-onset motor dysfunction (as measured by rotarod performance) accompanied by a loss of hindlimb-grip strength and the appearance of muscle fasciculations. Pathologically, Prp-TDP-43Q331K [~1.5x] mice demonstrate ~30% loss of L5 motor axons and 30-45% loss of lower motor neurons by ten months of age (earlier timepoints not yet tested; May 2012). Of note, this latter phenotype is in contrast to Dr. Robert Baloh's Prp-TDP43A315T transgenic mice that primarily display a loss of upper motor neurons (Stock No. 010700). Also note, this is in contrast to the founder line with low huTDP-43*Q331K overexpression (Prp-TDP-43Q331K-low line 109; Stock No. 017930), that do not exhibit loss of motor axons or neurons.

Development
A full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence was modified to have both an N-terminal myc tag and the glutamine to lysine substitution at amino acid 331 associated with familial ALS (huTDP-43*Q331K). This huTDP-43*Q331K cDNA sequence was inserted between exon 2 and exon 3 of mouse prion protein (PrP or Prnp) gene at two unique XhoI sites in the MoPrP.XhoI plasmid vector (ATCC#JHU-2). The resulting MoPrP.XhoI-mychuTDP-43*Q331K transgene was flanked with loxP sites, and then injected into the pronuclei of fertilized C57BL6/C3H hybrid eggs, which were implanted into pseudopregnant female mice. Transgenic founder mice were bred to C57BL/6 mice, and founder line 103 was identified with ~2.5-fold greater total TDP-43 (~1.5-fold greater huTDP-43*Q331K) expression levels in spinal cord as compared to endogenous TDP-43 in non-transgenic mice. These Prp-TDP-43Q331K [~1.5x] transgenic mice were bred with C57BL/6NCrl females for at least nine generations prior to sending to The Jackson Laboratory Repository. Upon arrival, transgenic mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generations to establish The Jackson Laboratory Repository colony.

Control Information

  Control
   Noncarrier
   005304 C57BL/6NJ
 
  Considerations for Choosing Controls

Related Strains

View Amyotrophic Lateral Sclerosis (ALS)     (30 strains)

Strains carrying other alleles of Prnp
012938   129-Prnptm2Edin/J
016925   129;B6-Del(10Grin3b-Tmem259)1Zang Tg(Prnp-C19ORF6,-GFP)6Zhang/J
003960   129S6-Tg(Prnp-GFP/cre)1Blw/J
005866   B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
006006   B6.Cg-Tg(Prnp-APP)A-2Dbo/J
008596   B6.Cg-Tg(Prnp-Abca1)EHol/J
006005   B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax
007180   B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
007182   B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J
006823   B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J
010700   B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J
009337   B6.FVB-Tg(Prnp-RTN3)2Yanr/J
007002   B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax
008169   B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J
004479   B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J
018917   B6;SJL-Tg(Prnp-CCS)17Jlel/J
003378   B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J
008216   B6CBA(FVB)-Tg(Prnp-TBP*)71-16Xjl/J
008075   B6CBA-Tg(Prnp-TBP*)105Xjl/J
008083   B6CBA-Tg(Prnp-TBP*)13Xjl/J
003741   B6D2-Tg(Prnp-MAPT)43Vle/J
024841   B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J
017907   B6N.Cg-Tg(Prnp-TARDBP)96Dwc/J
017930   B6N.Cg-Tg(Prnp-TARDBP*Q331K)109Dwc/J
025402   B6SJL-Tg(Prnp-Immt/SOD1)1Gmnf/J
025403   B6SJL-Tg(Prnp-Immt/SOD1*G93A)7Gmnf/J
016201   B6SJL-Tg(Prnp-TARDBP)4Jlel/J
016203   B6SJL-Tg(Prnp-TARDBP*A315T)23Jlel/J
016608   C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J
017604   C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J
019517   FVB-Tg(Prnp-HSPB1)1Kolb/J
019482   FVB-Tg(Prnp-HSPB1*R136W)1Kolb/J
018122   FVB.129S7(B6)-Prnptm1Cwe/J
017678   FVB;129-Pink1tm1Aub Tg(Prnp-SNCA*A53T)AAub/J
017744   FVB;129-Tg(Prnp-SNCA*A53T)AAub/J
017916   STOCK Tg(Prnp-FUS)WT3Cshw/J
016144   STOCK Tg(Prnp-TARDBP)4Jlel/J
016143   STOCK Tg(Prnp-TARDBP*A315T)23Jlel/J
008212   STOCK Tg(SMN2)89Ahmb Smn1tm1Msd Tg(Prnp-SMN)92Ahmb/J
View Strains carrying other alleles of Prnp     (39 strains)

View Strains carrying other alleles of TARDBP     (13 strains)

Additional Web Information

Working with ALS Mice manual [.pdf]
This resource was prepared by scientists with Prize4Life and The Jackson Laboratory.

Introduction to Cre-lox technology

Visit the Amyotrophic Lateral Sclerosis (ALS) Mouse Model Resource site for helpful information on ALS Disease and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Amyotrophic Lateral Sclerosis 10, with or without Frontotemporal Dementia;   (TARDBP)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Tg(Prnp-TARDBP*Q331K)103Dwc/?

        involves: C57BL/6 * C3H
  • behavior/neurological phenotype
  • decreased grip strength
    • in hind limbs   (MGI Ref ID J:191785)
  • impaired coordination
    • motor deficits appear by 3 months when tested on a rotarod   (MGI Ref ID J:191785)
  • limb grasping
    • hind limb clasping develops by 3 months of age   (MGI Ref ID J:191785)
  • tremors
    • develop tremors around 3 months of age   (MGI Ref ID J:191785)
  • muscle phenotype
  • abnormal muscle physiology   (MGI Ref ID J:191785)
    • abnormal muscle electrophysiology
      • spontaneous gastrocnemius muscle fibrillations   (MGI Ref ID J:191785)
      • reduced myogenic motor evoked potentials after stimulation of motor cortex   (MGI Ref ID J:191785)
    • abnormal muscle regeneration
      • regions of damaged muscle fibers and other areas of regeneration   (MGI Ref ID J:191785)
  • skeletal muscle degeneration
    • regions of damaged muscle fibers and other areas of regeneration   (MGI Ref ID J:191785)
  • nervous system phenotype
  • abnormal nervous system electrophysiology
    • no differences from controls recorded at the thoracic T12 segment after stimulation of motor cortex   (MGI Ref ID J:191785)
  • abnormal nervous system morphology   (MGI Ref ID J:191785)
    • abnormal neuromuscular synapse morphology
      • reduced number of gastrocnemius neuromuscular junction endplates   (MGI Ref ID J:191785)
    • abnormal spinal cord white matter morphology   (MGI Ref ID J:191785)
      • abnormal spinal cord dorsal column morphology
        • minor degeneration   (MGI Ref ID J:191785)
      • abnormal spinal cord lateral column morphology
        • minor degeneration   (MGI Ref ID J:191785)
    • decreased motor neuron number
      • age dependent decrease in motor neuron number of about 35%   (MGI Ref ID J:191785)
      • most significant reductions in large caliber alpha motor axons at 10-12 months   (MGI Ref ID J:191785)
View Research Applications

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

Neurobiology Research
Amyotrophic Lateral Sclerosis (ALS)
Ataxia (Movement) Defects
Cortical Defects
Cre-lox System
      loxP-flanked Sequences
Myelination Defects
Neurodegeneration
Neuromuscular Defects
Tremor Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Prnp-TARDBP*Q331K)103Dwc
Allele Name transgene insertion 103, Don W Cleveland
Allele Type Transgenic (Inserted expressed sequence)
Common Name(s) Prp-TDP-43Q331K;
Strain of OriginC57BL/6 x C3H
Expressed Gene TARDBP, TAR DNA binding protein, human
Promoter Prnp, prion protein, mouse, laboratory
Molecular Note A full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence was modified to have both an N-terminal myc tag and the glutamine to lysine substitution at amino acid 331 associated with familial ALS (huTDP-43*Q331K). This huTDP-43*Q331K cDNA sequence was inserted between exon 2 and exon 3 of mouse prion protein (Prnp) gene. The resulting Prnp-TDP-43*Q331K transgene was flanked with loxP sites. Founder line 103 was identified with approxiamately 2.5-fold greater total TDP-43 (1.5-fold greater huTDP-43*Q331K) expression levels in spinal cord as compared to endogenous TDP-43 in non-transgenic mice. [MGI Ref ID J:191785]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

** human TARDBP*Q331K, Pyrosequencing
Tg(Prnp-TARDBP*)Dwc,

MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Arnold ES; Ling SC; Huelga SC; Lagier-Tourenne C; Polymenidou M; Ditsworth D; Kordasiewicz HB; McAlonis-Downes M; Platoshyn O; Parone PA; Da Cruz S; Clutario KM; Swing D; Tessarollo L; Marsala M; Shaw CE; Yeo GW; Cleveland DW. 2013. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci U S A :. [PubMed: 23382207]  [MGI Ref ID J:191785]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB27

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice may be bred with wildtype (noncarrier) mice from the colony or with C57BL/6NJ inbred mice (Stock No. 005304). The donating investigator has not attempted to generate homozygous mice to date (May 2012).
Mating SystemNoncarrier x Hemizygote         (Female x Male)   01-OCT-12
Hemizygote x Noncarrier         (Female x Male)   01-OCT-12
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 $232.00Female or MaleHemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc  
Price per Pair (US dollars $)Pair Genotype
$304.00Hemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc x Noncarrier  
$304.00Noncarrier x Hemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc  

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 $301.60Female or MaleHemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc  
Price per Pair (US dollars $)Pair Genotype
$395.20Hemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc x Noncarrier  
$395.20Noncarrier x Hemizygous for Tg(Prnp-TARDBP*Q331K)103Dwc  

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
   Noncarrier
   005304 C57BL/6NJ
 
  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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