Strain Name: |
FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J |
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Stock Number: |
005025 |
Availability: | Repository- Live |
General Terms and Conditions |
| Strain Common Names | Moderate Type II SMA mice; SMNdelta7;SMN2;Smn-/-; |
| Genes & Alleles | SMN2; Smn1; Smn1tm1Msd; Tg(SMN2)89Ahmb; Tg(SMN2*delta7)4299Ahmb; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Type JAX® GEMM® Strain - Transgenic Mating System See Colony Maintenance (Female x Male) Species laboratory mouse Donating Investigator Arthur Burghes, The Ohio State University Generation N6+F9 (05-DEC-07) Strain Description
This triple mutant mouse harbors two transgenic alleles and a single targeted mutant. The Tg(SMN2*delta7)4299Ahmb allele consists of a SMA cDNA lacking exon 7 whereas the Tg(SMN2)89Ahmb allele consists of the entire human SMN2 gene. Mice that are homozygous for the targeted mutant Smn allele and homozygous for the two transgenic alleles exhibit symptoms and neuropathology similar to patients afflicted with proximal spinal muscular atrophy (SMA). At birth, triple mutants are noticeably smaller than normal littermates. By day 5, signs of muscle weakness are apparent and become progressively more pronounced over the following week as the mice display an abnormal gait, shakiness in the hind limbs and a tendency to fall over. Mean survival is approximately 13 days. Immunocytochemical analysis indicates that dystrophin expression is normal, however fibers isolated from the gastrocnemius muscle of a 14 day old triple mutant clearly show evidence of atrophy.Importation of this model was supported by the Spinal Muscular Atrophy Foundation. Creation and development was supported by the National Institutes of Health, the Deutsche Forschungsgemeinschaft to M.S., Families of SMA, the Preston fund, the Madison fund, the Mathew fund and the Muscular Dystrophy Association of America.
Strain Development
The targeted mutant allele was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the endogenous mouse Smn gene was disrupted by employing a targeting vector encoding 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. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations.
The transgenic alleles were created in the laboratory of Dr. Arthur Burghes at 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 animal 89 was obtained. Similarly, a human SMN2 cDNA (SMNdelta7) lacking exon 7 under the control of the human SMN2 promoter was microinjected into fertilized FVB/N oocytes and founder animal 4299 was obtained. Founder animal 89 was mated to mice heterozygous for the targeted mutation of the endogenous mouse Smn gene. These double mutants were in turn mated with mice bearing the SMNdelta7 transgenic allele. The triple mutant was then backcrossed to FVB/N for at least 6 generations.
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 | ||
| Site of Expression | The expression of the lacZ gene in tissues where Smn is normally expressed was noted. | ||
| 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(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 | ||
| Site of Expression | Dendrites, axons, and soma of spinal motor neurons display distinct expression of GFP. GFP expression mimics endogenous HLXB9 expression pattern. Fluorscence is detected in axons, dendrites, and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice. | ||
| 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] | ||
| Allele Symbol | Tg(SMN2*delta7)4299Ahmb | ||
| Allele Name | transgene insertion 4299, Arthur H M Burghes | ||
| Common Name(s) | SMNdelta7; Tg(SMN1*delta7)4299Ahmb; | ||
| Mutation Made By | Arthur Burghes, Ohio State University | ||
| Strain of Origin | FVB/N | ||
| Site of Expression | Dendrites, axons, and soma of spinal motor neurons display distinct expression of GFP. GFP expression mimics endogenous HLXB9 expression pattern. Fluorscence is detected in axons, dendrites, and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice. | ||
| Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human | ||
| Promoter | SMN2, survival of motor neuron 2, centromeric, human | ||
| Molecular Note | The transgene contains a human SMN2 promoter and a human SMN2 cDNA (SMNdelta7) that lacks exon 7. [MGI Ref ID J:97103] | ||
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | (approximate) | |
| Appropriate controls depend on the nature of the experiment. FVB/NJ mice (Stock No. 001800) may be used as controls. | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Smn1tm1Msd
Tg(SMN2)89Ahmb
Tg(SMN2*delta7)4299Ahmb
Tg(SMN2*delta7)4299Ahmb QPCR
Colony Maintenance
| Breeding & Husbandry | The Smn1 (survival motor neuron 1) gene on Chr 13 and the two randomly inserted transgenes are not linked and will segregate independently. Breeding pairs offered by The Jackson Laboratory are homozygous for the two transgenes and heterozygous for the targeted Smn mutation. These breeding pairs are phenotypically normal and do not exhibit symptoms of neuropathology. Offspring resulting from the mating of breeder pairs can posses the following genotypes: 1. Homozygous for both transgenes and homozygous for the targeted mutation (25%) Mice that are homozygous for both transgenes and homozygous for the targeted mutation will display the SMA-like phenotype. Mice homozygous for both transgenes and heterozygous for the targeted mutation will not display the SMA-like phenotype but can be mated with each other to generate additional affected mice. Mice homozygous for both transgenes and wildtype at the Smn1 locus will also not exhibit an SMA-like phenotype but can be employed as control mice depending on the nature of the experiment. |
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| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (174 strains)
007951 STOCK Smn1tm3(SMN2/Smn1)Mrph Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb/J
008206 FVB.Cg-Smn1tm1Msd Tg(SMN2)566Ahmb/J 005058 FVB.Cg-Tg(SMN2)2Hung Smn1tm1Hung/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Genetic Quality Control Annual Report
Animal Health Reports
Room Number AX12
Research Applications
This mouse can be used to support research in many areas including:
Smn1tm1Msd relatedNeurobiology Research
Neurodegeneration
Neuromuscular Defects
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 ReferencesLe TT; Pham LT; Butchbach ME; Zhang HL; Monani UR; Coovert DD; Gavrilina TO; Xing L; Bassell GJ; Burghes AH. 2005. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14(6):845-57. [PubMed: 15703193] [MGI Ref ID J:97103]
Price and Supply Information
| Strain Name: | FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J |
| Stock Number: | 005025 |
Price Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource. |
| Licensing | See General Terms and Conditions below for Licensing and Use Restrictions |
| Control Information | View Control Information in Strain Details. |
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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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