| |||||||||||||||
| 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
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating 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 develop a progressive gait disorder around 3-4 months of age, and die around 5 months of age. This progressive and fatal neurodegenerative disease 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, and also reports that mice are black or agouti.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 Prp-TDP43A315T founder line was established (founder line 95). These mice were then backcrossed to C57BL/6J inbred mice for five generations prior to arrival at The Jackson Laboratory. The donating investigator reports that mice are black or agouti. Upon arrival, transgenic mice were bred with C57BL/6J inbred mice (Stock No. 000664) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Prnp
View Strains carrying other alleles of Prnp (20 strains)
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Prnp-TARDBP*A315T)95Balo/0
involves: C57BL/6 * CBA
- life span-post-weaning/aging
- premature death (MGI Ref ID J:153197)
- average survival is 154 days; at end-stage, mice die spontaneously or are euthanized when they lose righting reflex or can no longer obtain food and water
- growth/size phenotype
- weight loss (MGI Ref ID J:153197)
- mice begin losing weight around 4.5 months of age
- behavior/neurological phenotype
- abnormal gait (MGI Ref ID J:153197)
- at 3-4 months mice develop abnormal gait; around 4.5 months, mice exhibit a "swimming" gait when they lose ability to support their body weight but still use their limbs for propulsion to slide on their stomachs
- nervous system phenotype
- abnormal neuron morphology (MGI Ref ID J:153197)
- late-stage mice have cytoplasmic accumulation of ubiquinated proteins in neurons of cortical layer 5; these neurons are prominent in the motor cortex and are also present in orbital, cingulated, sensory and other cortical regions
- no ubiquinated protein aggregates are observed in the caudate/putamen, substantia nigra, thalamus or other structures at any stage
- decreased motor neuron number (MGI Ref ID J:153197)
- in end-stage mice, about a 20% loss of spinal motor neurons is observed
- neuron degeneration (MGI Ref ID J:153197)
- neuron loss in cortical layer 5
- motor neuron degeneration (MGI Ref ID J:153197)
- fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
- femoral motor and sensory nerves shows loss of axons with ongoing axonal degeneration in the motor branch
- abnormal spinal cord morphology (MGI Ref ID J:153197)
- fewer axons are observed in the lower thoracic spinal cord with numerous degenerating axons being seen in dorsal corticospinal tract and lateral columns
- abnormal spinal cord ventral horn morphology (MGI Ref ID J:153197)
- presence of ubiquitinated protein accumulations is detected preferentially in large neurons of the dorsal horn as well as scattered interneurons
- decreased motor neuron number (MGI Ref ID J:153197)
- in end-stage mice, about a 20% loss of spinal motor neurons is observed
- astrocytosis (MGI Ref ID J:153197)
- activation of astrocytes is detected in layer 5 with reactive astrocytosis seen around degenerating neurons
- muscle phenotype
- abnormal muscle electrophysiology (MGI Ref ID J:153197)
- electromyography in end-stage mice shows numerous fibrillation potentials indicative of loss of muscle fiber innervation and fasciculations, which are spontaneous firing of motor units often seen with human motor neuron diseases; in presymptomatic and early-stage mice, electromyography is normal
- abnormal skeletal muscle morphology (MGI Ref ID J:153197)
- end-stage mice have scattered and grouped atrophic muscle fibers, characteristic of muscle denervation
- abnormal skeletal muscle fiber morphology (MGI Ref ID J:153197)
- atrophic muscle fibers are observed in end-stage mice
- muscle weakness (MGI Ref ID J:153197)
- around 4.5 months, mice can no longer support their body weight
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
| 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
Tg(Prnp-TARDBP*A315T), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
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
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). The donating investigator has not attempted to make homozygous mice, and also reports that mice are black or agouti.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Production.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date:
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
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.Ordering and Purchasing Information
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"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.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. In purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.