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| Prp-TDP43A315T transgenic mice express a mutant human TAR DNA binding protein cDNA harboring an amino acid substitution associated with familial ALS. Hemizygous mice develop a progressive and fatal neurodegenerative disease reminiscent of both ALS and frontotemporal lobar degeneration with ubiquitin aggregates. These transgenic mice may be useful in studying neuromuscular and neurodegenerative disorders such as ALS (Lou Gehrig's Disease) and frontotemporal lobar degeneration with ubiquitin aggregates. | |||||||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6;CB-Tg(Prnp-TARDBP*A315T)95Balo/J (Changed: 23-MAR-11 ) B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J (Changed: 22-DEC-09 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Noncarrier x Hemizygote (Female x Male) 26-MAR-10 Mating System Hemizygote x Noncarrier (Female x Male) 06-FEB-12 Species laboratory mouse Generation N5+N8 (11-JUL-11)
Generation DefinitionsDonating Investigator Robert Baloh, Washington University School of Medicine Description
Mice hemizygous for this Prp-TDP43A315T transgene are viable, fertile, and express a mutant human TAR DNA binding protein (TARDBP or TDP-43) cDNA harboring an N-terminal Flag tag and an A315T amino acid substitution that is associated with familial Amyotrophic Lateral Sclerosis (ALS). Expression is directed throughout the nervous system by mouse prion protein (PrP or Prnp) promoter/enhancer regions.Hemizygous mice were originally published on a mixed C57BL/6;CBA genetic background and develop a progressive gait disorder around 3-4 months of age with death around 5 months of age. For hemizygous mice on a mixed C57BL/6;CBA genetic background, the donating investigator reports that, on average, males die almost one month earlier than females. Due to continued backcrossing to C57BL/6J at The Jackson Laboratory Repository, this strain is now fully congenic on a C57BL/6J background. Survival differences between male and female hemizygous mice are still observed. However, hemizygous males on a C57BL/6J genetic background have an average survival time of approximately 3.5 months (97 +/- 11 days); this is earlier lethality than hemizygous males on a mixed C57BL/6;CBA genetic background. On a C57BL/6J genetic background, hemizygous females live significantly longer than hemizygous males. For more detailed information, please view graph of B6.Tg(Prnp-TARDBP*A315T)95Balo/J survival and data 2010-2022. [pdf]
The progressive and fatal neurodegenerative disease phenotype of hemizygous mice is reminiscent of both ALS and frontotemporal lobar degeneration with ubiquitin aggregates (FTLD-U). Specifically, hemizygous mice accumulate pathologic aggregates of ubiquitinated proteins only in specific neuronal populations, including frontal cortex layer V pyramidal neurons and spinal motor neurons with activation of local astrocytes and microglia. Loss of both upper and lower motor neurons is also observed. TDP-43 aggregates are not reported in the cytoplasm. The donating investigator has not attempted to make homozygous mice.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As the Prp-TDP43A315T transgenic mice were originally created on a mixed C57BL/6;CBA genetic background, it should be noted that the phenotype of these Prp-TDP43A315T transgenic mice on a C57BL/6-congenic background may vary greatly from that originally described. We will modify the strain description if necessary as published results become available.
Development
A full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence was modified to harbor an N-terminal Flag tag immediately after the start methionine and the A315T amino acid substitution associated with familial ALS. This Flag-TDP43A315T sequence was inserted between exon 2 and exon 3 of mouse prion protein (PrP or Prnp) gene at two unique XhoI sites in the Mo-Prp.Xho plasmid vector (ATCC#JHU-2). The resulting Prp-TDP43A315T transgene was microinjected into oocytes from hybrid C57BL/6J x CBA mice and a single founder mouse was bred with C57BL/6 wildtype mice to establish Prp-TDP43A315T founder line 95. These mice were then backcrossed to C57BL/6J inbred mice for approximately five generations (with black or agouti coat color) prior to sending agouti mice to The Jackson Laboratory Repository. Upon arrival, transgenic mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony. A subsequent genome scan revealed this stock to be approximately 80% congenic to C57BL/6J. After this, hemizygous mice were additionally backcrossed to C57BL/6J inbred mice for multiple generations to make the mice fully congenic on the C57BL/6J genetic background.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Amyotrophic Lateral Sclerosis (ALS)
009680 B6.B-Vps54wr/J 002298 B6.Cg-Tg(SOD1)2Gur/J 008229 B6.Cg-Tg(SOD1*G37R)29Dpr/J 008342 B6.Cg-Tg(SOD1*G37R)42Dpr/J 008248 B6.Cg-Tg(SOD1*G85R)148Dwc/J 004435 B6.Cg-Tg(SOD1*G93A)1Gur/J 002299 B6.Cg-Tg(SOD1*G93A)dl1Gur/J 002297 B6SJL-Tg(SOD1)2Gur/J 002726 B6SJL-Tg(SOD1*G93A)1Gur/J 002300 B6SJL-Tg(SOD1*G93A)dl1Gur/J 016201 B6SJL.Cg-Tg(Prnp-TARDBP)4Jlel/J 016608 C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J 017604 C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J 002628 C57BL/6-Tg(SOD1)10Cje/J 002629 C57BL/6-Tg(SOD1)3Cje/J 005706 C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J 008230 FVB(Cg)-Tg(Thy1-SOD1*G93A)T3Hgrd/J 005110 FVB-Tg(Sod1*G86R)M1Jwg/J 013199 FVB.Cg-Tg(SOD1*G93A)1Gur/J 013574 FVB/N-Tg(149m19)M141Kunst/J 016144 STOCK Tg(Prnp-TARDBP)4Jlel/J 016143 STOCK Tg(Prnp-TARDBP*A315T)23Jlel/J View Amyotrophic Lateral Sclerosis (ALS) (22 strains)
016841 B6;C3-Tg(tetO-TARDBP)12Vle/J 014650 B6;C3-Tg(tetO-TARDBP*)4Vle/J 012836 B6;SJL-Tg(Thy1-TARDBP)4Singh/J 016608 C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J 017604 C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J 016144 STOCK Tg(Prnp-TARDBP)4Jlel/J 016143 STOCK Tg(Prnp-TARDBP*A315T)23Jlel/J
Additional Web Information
Working with ALS Mice manual [.pdf]
This resource was prepared by scientists with Prize4Life and The Jackson Laboratory.
Visit the Amyotrophic Lateral Sclerosis (ALS) Mouse Model Resource site for helpful information on ALS Disease and research resources.
Phenotype
Phenotype Information
This mouse can be used to support research in many areas including:
Mouse/Human Gene Homologs
amyotrophic lateral sclerosis (ALS)
Neurobiology Research
Amyotrophic Lateral Sclerosis (ALS)
Astrocyte Defects
Ataxia (Movement) Defects
Neurodegeneration
Neuromuscular Defects
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Prnp-TARDBP*A315T)95Balo | ||
|---|---|---|---|
| Allele Name | transgene insertion 95, Robert Baloh | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Prp-TDP43-A315T; Prp-TDP43A315T; | ||
| Mutation Made By | Robert Baloh, Washington University School of Medicine | ||
| Strain of Origin | C57BL/6 x CBA | ||
| Expressed Gene | TARDBP, TAR DNA binding protein, human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| Molecular Note | The construct contains the full-length human TAR DNA binding protein (TARDBP or TDP-43) cDNA sequence that was modified to harbor an N-terminal Flag tag immediately after the start methionine and the A315T amino acid substitution associated with familial ALS inserted between exon 2 and exon 3 of mouse prion protein (PrP or Prnp) gene. The Prp-TDP43A315T transgene was microinjected into oocytes from hybrid C57BL/6J x CBA mice and a single Prp-TDP43A315T founder line was established (founder line 95). [MGI Ref ID J:153197] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Human TARDBP, QPCR
Tg(Prnp-TARDBP*A315T), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Wegorzewska I; Bell S; Cairns NJ; Miller TM; Baloh RH. 2009. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A :. [PubMed: 19833869] [MGI Ref ID J:153197]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous carriers may be bred with wildtype (noncarrier) mice from the colony or C57BL/6J inbred mice (Stock No. 000664). Hemizygous males on a C57BL/6J genetic background have an average survival time of approximately 3.5 months (97 +/- 11 days); this is earlier lethality than hemizygous males on a mixed C57BL/6;CBA genetic background. On a C57BL/6J genetic background, hemizygous females live significantly longer than hemizygous males. The donating investigator has not attempted to make homozygous mice. Mating System Noncarrier x Hemizygote (Female x Male) 26-MAR-10 Hemizygote x Noncarrier (Female x Male) 06-FEB-12 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $261.00 Female or Male Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo
Pairs /Price (US dollars $) Pair Genotype $280.40 C57BL/6J (000664) x Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo $279.00 Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo x C57BL/6J (000664) Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $339.30 Female or Male Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo
Pairs /Price (US dollars $) Pair Genotype $364.60 C57BL/6J (000664) x Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo $362.70 Hemizygous for Tg(Prnp-TARDBP*A315T)95Balo x C57BL/6J (000664) Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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