Strain Name: |
FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J |
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Stock Number: |
005026 |
Availability: | Repository- Live |
General Terms and Conditions |
| Strain Common Names | Mild Type III SMA; SMN A2G; |
| Genes & Alleles | SMN1; SMN2; Smn1; Smn1tm1Msd; Tg(SMN1*A2G)2023Ahmb; Tg(SMN2)89Ahmb; |
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 N6F?+5 (05-DEC-07) Strain Description
Mice that are homozygous for the targeted mutant Smn allele and homozygous for the SMN2transgene and hemizygous for the SMN1*A2G transgenes exhibit symptoms and neuropathology similar to patients afflicted with type III (mild) proximal spinal muscular atrophy (SMA). These same animals with only one copy of the SMN2transgene are 20%-40% smaller than unaffected mice. At 3 weeks of age they become less active and show signs of muscle weakness. The mice have a shortened lifespan (less than a year) near the end of which they exhibit reduced movement, diminished grooming, shallow breathing and considerable weight loss. Immunohistochemical analysis of spinal cord tissue from 1 month-old animals indicates the presence of cytoplasmic SMN protein and intranuclear aggregates (gems) of the SMN protein. The number of gems is however, fewer than the number found in age matched control tissues. Histological analysis of muscle tissue (gastrocnemius, quadriceps, and intercostals muscles) reveals numerous angulated and atrophic fibers. This trait is more pronounced in the gastrocnemius muscle tissue. Reduced numbers of motor neurons are observed in lumbar spinal cord (29% fewer) and facial nucleus (~19% fewer) tissues derived from 3.5-month-old triple mutant mice. Normal numbers of motor neurons are found in 5 day-old mice , indicating that motor neuron loss is a later event in SMA. Electromyograph (EMG) recordings from 4-6 month old triple mutants provide a clear indication of denervation. Associated compensatory axon sprouting is observed. Triple mutants homozygous for the SMN1 A2G transgene display a much milder phenotype, live longer and breed well. Hemizygotes can be bred, but are less efficient.Note: In contrast to the original publication, and possibly due to inbreeding, it is the experience at The Jackson Laboratory that mice hemizygous for the SMN2 transgene do not survive.
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 Smn 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 several 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 obtained. Similarly, a human SMN1 cDNA carrying the A2G missense mutation under the control of the human SMN1 promoter was microinjected into fertilized FVB/N oocytes and founder animal 2023, bearing 11 copies of the transgene, 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 SMN1 transgenic allele. The triple mutant was then backcrossed to FVB/N for at least 6 generations.
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 | ||
| 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(SMN1*A2G)2023Ahmb | ||
| Allele Name | transgene insertion 2023, Arthur H M Burghes | ||
| Common Name(s) | SMN A2G; | ||
| Mutation Made By | Arthur Burghes, Ohio State University | ||
| Strain of Origin | FVB/N | ||
| Site of Expression | The expression of the lacZ gene in tissues where Smn is normally expressed was noted. | ||
| Expressed Gene | SMN1, survival of motor neuron 1, telomeric, human | ||
| Promoter | SMN1, survival of motor neuron 1, telomeric, human | ||
| General Note | Hemizygous mice that are also hemizygous for Tg(SMN2)89Ahmb and homozygous for Smn1tm1Msd exhibit symptoms and neuropathology similar to patients afflicted with type III (mild) proximal spinal muscular atrophy (SMA). Triple mutants are 20%-40%smaller than unaffected mice. At 3 weeks of age they become less active and show signs of muscle weakness. The mice have a shortened lifespan (less than a year) near the end of which they exhibit reduced movement, diminished grooming, shallow breathing and considerable weight loss. Immunohistochemical analysis of spinal cord tissue from one month-old animals indicates the presence of cytoplasmic SMN protein and intranuclear aggregates (gems) of the SMN protein. Histological analysis of muscle tissue (gastrocnemius, quadriceps, and intercostals muscles) reveals numerous angulated and atrophic fibers. This trait is more pronounced in the gastrocnemius muscle tissue. Reduced numbers of motor neurons are observed in lumbar spinal cord (29% fewer) and facialnucleus (~19% fewer) tissues derived from 3.5-month-old triple mutant mice. Normal numbers of motor neurons are found in 5 day-old mice, indicating that motor neuron loss is a later event in SMA. Electromyograph (EMG) recordings from 4-6 month old triplemutants provide a clear indication of denervation. Associated compensatory axon sprouting is observed. Triple mutants homozygous for the SMN1 A2G transgene display a much milder phenotype, live longer and breed well. Hemizygotes can be bred, but are lessefficient. | ||
| Molecular Note | A 4.9 kb construct carrying a human SMN1 cDNA with an A2G missense mutation in exon 1, under control of the human SMN promoter, was used for the transgene. Line 2023 carries 11 copies of the transgene. [MGI Ref ID J:81238] | ||
| 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] | ||
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| 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(SMN1*A2G)2023Ahmb
Tg(SMN2)89Ahmb
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 will be made up of: (a) One mouse homozygous for both the SMN2 and SMN1 transgenes and heterozygous for the targeted Smn1 mutation. (b) One mouse homozygous for the SMN2 transgene and heterozygous for the targeted Smn1 mutation. This cross will produce a Type III SMA-like phenotype in mice that are homozygous for the SMN2 transgene; hemizygous for the SMN1 transgene and homozygous for the targeted mutation will display a Type III SMA-like phenotype at a frequency of 1 in 4. ***NOTE Mice that are homozygous for both transgenes and homozygous for the Smn1 mutation are reported to be fertile, although males are reportedly better breeders than females. However, The experience at The Jackson Laboratory is that these mice have a high incidence of non-productive matings when bred to mice homozygous for the SMN2 transgene and heterozygous for the targeted Smn1 mutation. NOTE: The experience at The Jackson Laboratory is that mice homozygous at all three loci have a high incidence of non-productive matings. Note: In contrast to the original publication, and possibly due to inbreeding, it is the experience at The Jackson Laboratory that mice hemizygous for the SMN2 transgene do not survive. |
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| Diet Information | LabDiet® 5K52/5K67 |
Related Strains
lacZ Expression 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 008212 STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Animal Health Reports
Room Number AX12
Research Applications
This mouse can be used to support research in many areas including:
Smn1tm1Msd relatedNeurobiology Research
Ataxia (Movement) Defects
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 ReferencesMonani UR; Pastore MT; Gavrilina TO; Jablonka S; Le TT; Andreassi C; DiCocco JM; Lorson C; Androphy EJ; Sendtner M; Podell M; Burghes AH. 2003. A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy. J Cell Biol 160(1):41-52. [PubMed: 12515823] [MGI Ref ID J:81238]
Price and Supply Information
| Strain Name: | FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J |
| Stock Number: | 005026 |
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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