Strain Name: |
STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J |
|---|---|
Stock Number: |
008212 |
Availability: | Under Development for Distribution Colony |
| To register your interest in this strain go to the Strain Interest Form. |
General Terms and Conditions |
| Genes & Alleles | Prnp; SMN1; SMN2; Smn1; Smn1tm1Msd; Tg(Prnp-SMN)92Ahmb; Tg(SMN2)89Ahmb; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Type JAX® GEMM® Strain - Transgenic Species laboratory mouse Donating Investigator Arthur Burghes, The Ohio State University Strain Description
As described for SMA mice (see Stock No. 005024), mice homozygous for Smn1tm1Msd targeted mutation (Smn null allele) and human SMN2 transgene (SMN2 low copy line 89) exhibit symptoms, neuropathology, and early lethality similar to human type I proximal spinal muscular atrophy (SMA) patients. As an addition to that SMA model, this strain also carries the PrP-SMN transgene; with the mouse prion protein (PrP or Prnp) promoter directing full-length human SMN expression at high levels in neurons (with low expression in skeletal muscle and liver). When the PrP-SMN transgene is derived from PrP92-SMN founder mice, high SMN expression in spinal cord and brain is observed. Homozygous SMN2; Smn; Prp92-SMN mice are rescued from the severe SMA phenotype, have significantly increased lifespan (average of 210 days) and have normal lumbar motor neuron root counts. Homozygous SMN2; Smn; PrP92-SMN males are infertile, females are fertile but poor mothers, and both sexes exhibit necrotic tail development with about one-third of the normal length remaining around the time of weaning. These SMN2; Smn; PrP92-SMN mutant mice may be useful in neuromuscular studies including spinal muscular atrophy (SMA).Strain Development
These SMN2; Smn; PrP92-SMN mutant mice harbor a targeted mutation and two trangenes, all independently created.The Smn1tm1Msd targeted mutation was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the targeted gene was disrupted with a neomycin cassette and a lacZ gene (fused to the first 40 nucleotides of the disrupted exon to permit expression of the lacZ gene in tissues where Smn is normally expressed). The construct was electroporated into 129P2/OlaHsd-derived E14Tg2a-IV embryonic stem (ES) cells. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations.
The PrP-SMN transgene was designed with the mouse prion protein gene (PrP or Prnp) promoter region and exon 1 and 2, full-length SMN cDNA (containing exons 1-8), and two SV40 polyA signals. This transgene was microinjected into fertilized FVB/N oocytes. Mice from founder line 92 (PrP92-SMN) were found to have 8-9 copies of the transgene.
The SMN2 transgene was created in the laboratory of Dr. Arthur Burghes at The Ohio State University. A 35.5 kb BamHI genomic fragment encoding the human SMN2 promoter and gene (derived from genomic clone PAC215P15) was injected into fertilized FVB/N mouse oocytes and founder animals obtained. Transgenic SMN2 mice from founder line 89 were established and found to contain one copy of the transgene (also called SMN2 low copy line 89).
These SMN2; Smn; PrP92-SMN mutant mice (heterozygous for the targeted mutation and homozygous for both transgenes) were maintained on a mixed genetic background (mostly FVB/N and C57BL/6) for many generations prior to arrival at The Jackson Laboratory.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Smn1tm1Msd | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Michael Sendtner | ||
| Common Name(s) | SMN-; | ||
| Mutation Made By | Michael Sendtner, | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14Tg2aIV | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Smn1, survival motor neuron 1 | ||
| Chromosome | 13 | ||
| Gene Common Name(s) | AI849087; BCD541; SMA; SMA1; SMA2; SMA3; SMA4; SMA@; SMN; SMNT; Smn; T-BCD541; expressed sequence AI849087; survival motor neuron; | ||
| Molecular Note | A lacZ-neo cassette was inserted into exon 2 by homologous recombination resulting in an in-frame fusion of lacZ to exon 2. Homozygous mutant embryos were identified up to 80 hours post coitum. The expression of the lacZ gene in tissues where Smn is normally expressed was noted. [MGI Ref ID J:42813] | ||
| Allele Symbol | Tg(Prnp-SMN)92Ahmb | ||
| Allele Name | transgene insertion 92, Arthur H M Burghes | ||
| Common Name(s) | PrP92-SMN; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | SMN1, survival of motor neuron 1, telomeric, human | ||
| Promoter | Prnp, prion protein, mouse, laboratory | ||
| Molecular Note | The PrP-SMN transgene was designed with the mouse prion protein gene (PrP or Prnp) promoter region and exon 1 and 2, full-length SMN cDNA (containing exons 1-8), and two SV40 polyA signals. Mice from founder line 92 (PrP92-SMN) were found to have 8-9 copies of the transgene. [MGI Ref ID J:131663] | ||
| Allele Symbol | Tg(SMN2)89Ahmb | ||
| Allele Name | transgene insertion 89, Arthur H M Burghes | ||
| Common Name(s) | SMN2; | ||
| Mutation Made By | Arthur Burghes, Ohio State University | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human | ||
| Promoter | SMN2, survival of motor neuron 2, centromeric, human | ||
| Molecular Note | A 35.5 kb genomic fragment containing the human survival motor neuron 2 (SMN2) gene and promoter was used for the transgene. The transgene is ubiquitously expressed in all tissues examined by Northern blot analysis. Line 89 carries 1 copy of the transgene. [MGI Ref ID J:60592] | ||
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Smn1tm1Msd
Tg(SMN2)89Ahmb
Colony Maintenance
| Breeding & Husbandry | When maintaining a live colony, mice heterozygous for the Smn1tm1Msd targeted mutation, homozygous for the SMN2 low copy line 89 transgene, and homozygous for the PrP92-SMN transgene are bred together. The donating investigator reports that mice homozygous for all three mutations are poor breeders (males infertile, females poor mothers). The SMN2 low copy line 89 transgene is reported to have a single copy (thus homozygotes have 2 copies). The PrP92-SMN transgene copy number should be monitored as the phenotype of SMA models may be greatly affected by copy number variations. |
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Related Strains
lacZ Expression Strains
View lacZ Expression Strains (174 strains)
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008203 FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)63Ahmb Tg(SMN2)89Ahmb/J 008209 FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)69Ahmb Tg(SMN2)89Ahmb/J 005026 FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Research Applications
This mouse can be used to support research in many areas including:
Smn1tm1Msd relatedDevelopmental Biology Research
Neurodevelopmental Defects
Neurobiology Research
lacZ expression in neural tissue
Ataxia (Movement) Defects
Neurodegeneration
Neurodevelopmental Defects
Neuromuscular Defects
Spinal Muscular Atrophy (SMA)
Research Tools
lacZ Expression
Genetics Research (Tissue/Cell Markers: multiple)
Genetics Research (Tissue/Cell Markers: neurons)
Neurobiology Research (cell marker)
Neurobiology Research
Spinal Muscular Atrophy (SMA)
References
Selected Reference(s)
Additional ReferencesGavrilina TO; McGovern VL; Workman E; Crawford TO; Gogliotti RG; Didonato CJ; Monani UR; Morris GE; Burghes HM. 2008. Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle specific SMN expression has no phenotypic effect. Hum Mol Genet :. [PubMed: 18178576] [MGI Ref ID J:131663]
Price and Supply Information
| Strain Name: | STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J |
| Stock Number: | 008212 |
This strain is currently Under Development for Distribution Colony.
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.
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Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
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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.Ordering and Purchasing Information
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