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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Transgenic; Mating System See Colony Maintenance Species laboratory mouse Generation N5+2F7 (05-DEC-07) Donating Investigator Hung Li, Institute of Molecular Biology Description
Mice that are homozygous for the Smn1 targeted mutation and hemizygous for the SMN2 transgene are viable, fertile and exhibit short and thickened tails. RT-PCR analysis detects alternative splicing of the transgene. Histological examination of tail tissue reveals atrophic muscles and subcutaneous edema. Skeletal muscle tissue has fewer myocytes and atrophic muscle bundles. Large motor neurons in the anterior horns of the spinal cord degenerate and are lost. There is a strong correlation between estimated copy number of the transgene and severity of the phenotype. These mice exhibit a molecular and progressive neurodegenerative phenotype similar to Type III spinal muscular atrophy. Mice that are homozygous for the targeted mutation and do not carry the transgene have an embryonic lethal phenotype, failing to survive past embryonic day 6.5.Importation of this model was supported by the Spinal Muscular Atrophy Foundation.
Development
Double mutant mice were generated by crossing transgenic mice carrying the human SMN2 gene with mice heterozygous for the Smntm1Hung targeted mutation. The targeted mutant allele was generated by disrupting exon 7 with a vector containing neomycin resistance and herpes simplex virus thymidine kinase genes. This construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for more than 5 generations. The transgene consists of 115kb of sequence from the SMN BAC clone 7C, including the entire human SMN2 coding region and flanking sequence. The transgenic construct was microinjected into male pronuclei of FVB/N mice. Founder line 2 was crossed to mice heterozygous for the targeted mutation, Smntm1Hung. The double mutant was then backcrossed to FVB/N for 5 generations.
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Appropriate controls depend on the nature of the experiment. FVB/NJ mice (Stock No. 001800) may be included among the controls considered. | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of SMN2
View Strains carrying other alleles of SMN2 (9 strains)
Additional Web Information
Congenic Nomenclature
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
Related Disease (OMIM) Terms
Spinal Muscular Atrophy, Type I; SMA1 Mammalian Phenotype Terms assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Smn1tm1Hung/Smn1tm1Hung Tg(SMN2)2Hung/Tg(SMN2)2Hung
involves: 129P2/OlaHsd * FVB/N
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:59313)
- mice with the most severe phenotype (type 1) die before P10
- mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks
- mice with a mild phenotype (type 3) live a normal lifespan
- life span-post-weaning/aging
- premature death (MGI Ref ID J:59313)
- mice with an intermediate phenotype (type 2) die at approximately 2-4 weeks
- nervous system phenotype
- abnormal astrocyte morphology (MGI Ref ID J:59313)
- presence of glial bundles observed in anterior spinal root of type 1 mice
- abnormal motor neuron morphology (MGI Ref ID J:59313)
- selective loss of thick myelinated fibers observed in anterior spinal root of type 1 mice
- decreased motor neuron number (MGI Ref ID J:59313)
- loss of large motor neurons in anterior horns of spinal cord with appearance of empty cell beds
- phenotype is not observed in type 3 mice
- axon degeneration (MGI Ref ID J:59313)
- exhibited in anterior spinal roots
- phenotype is not observed in type 3 mice
- chromatolysis (MGI Ref ID J:59313)
- exhibited in motor neurons of anterior horn of type 1 mice
- muscle phenotype
- abnormal skeletal muscle fiber morphology (MGI Ref ID J:59313)
- decreased diameter of muscle fibers in tail
- fewer muscle fibers and atrophic muscle bundles in trunk and limb muscles
- skeletal muscle fiber hypertrophy (MGI Ref ID J:59313)
- atrophic fibers associated with hypertrophic type 1 fibers in type 1 mice
- muscular atrophy (MGI Ref ID J:59313)
- atrophy of muscle bundles in tail, trunk and limb muscles
- limbs/digits/tail phenotype
- abnormal tail morphology (MGI Ref ID J:59313)
- decreased diameter of muscle fibers, atrophy of muscle bundles, group atrophy and subcutaneous edema
- edema is more severe in type 3 than in type 2 mice and rare in type 1 mice
- short tail (MGI Ref ID J:59313)
- exhibited by mice with the type 3 phenotype
- thick tail (MGI Ref ID J:59313)
- exhibited by mice with the type 3 phenotype
- homeostasis/metabolism phenotype
- extremity edema (MGI Ref ID J:59313)
- subcutaneous edema of tail, most severe in type 3 mice and rare in type 1
- subcutaneous edema of hindlimbs
- behavior/neurological phenotype
- hindlimb paralysis (MGI Ref ID J:59313)
- exhibited in some type 2 mice
- cellular phenotype
- necrosis (MGI Ref ID J:59313)
- 50% of type 1 and 2 mice develop chronic necrosis from the tip of the tail to the root
- growth/size phenotype
- decreased body weight (MGI Ref ID J:59313)
- exhibited by all three phenotypes, decrease is proportionate to severity of symptoms
- skin/coat/nails phenotype
- nude (MGI Ref ID J:59313)
- type 1 mice do not develop fur
Research Applications
This mouse can be used to support research in many areas including:
Smn1tm1Hung relatedNeurobiology Research
Ataxia (Movement) Defects
Neurodegeneration
Neuromuscular Defects
Neurobiology Research
Spinal Muscular Atrophy (SMA)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Smn1tm1Hung | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Hung Li | ||
| Common Name(s) | Smn-; | ||
| Mutation Made By | Hung Li, Institute of Molecular Biology | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14TG2a | ||
| 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; | ||
| General Note |
Homozygous mutant mice died during the peri-implantation stage. In contrast, homozygous mutant mice carrying Tg(SMN2)1Hung display pathological changes in the spinal cord and skeletal muscles similar to those of patients with proximal spinal muscular atrophy (SMA). Some of these mice do not develop hairy fur, and die before postnatal day 10. Others exhibit poor activity and variable symptoms, and die at approximately 2-4 weeks. A third group of these mice survive to adulthood and are fertile, but have short enlarged tails. The variable severity of the pathological changes in these mice correlates with transgene copy number and the amount of protein that contains the region encodedby exon 7. | ||
| Molecular Note | Exon 7 was replaced with an HPRT cassette via homologous recombination. Homozygous embryos were detected at E3.5 but not after E6.5. [MGI Ref ID J:59313] | ||
| Allele Symbol | Tg(SMN2)2Hung | ||
| Allele Name | transgene insertion 2, Hung Li | ||
| Common Name(s) | SMN2+; | ||
| Mutation Made By | Hung Li, Institute of Molecular Biology | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human | ||
| Promoter | SMN2, survival of motor neuron 2, centromeric, human | ||
| General Note |
Five lines were generated. Hemizygous transgenic mice that are also homozygous for Smn1tm1Hung display:
| ||
| Molecular Note | The transgene consists of 115kb of sequence from the SMN BAC clone 7C, including the entire human SMN2 coding region and flanking sequence. [MGI Ref ID J:59313] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Smn tm1Hung/J, , vers. 1
Smn1tm1Hung, STD PCR, vers. 1
Tg(SMN2)2Hung QPCR, QPCR, vers. 2
Tg(SMN2)2Hung, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Hsieh-Li HM; Chang JG; Jong YJ; Wu MH; Wang NM; Tsai CH; Li H. 2000. A mouse model for spinal muscular atrophy. Nat Genet 24(1):66-70. [PubMed: 10615130] [MGI Ref ID J:59313]
Additional References
Chang JG; Hsieh-Li HM; Jong YJ; Wang NM; Tsai CH; Li H. 2001. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808-13. [PubMed: 11504946] [MGI Ref ID J:94612]
Smn1tm1Hung related
Chang JG; Hsieh-Li HM; Jong YJ; Wang NM; Tsai CH; Li H. 2001. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808-13. [PubMed: 11504946] [MGI Ref ID J:94612]Tg(SMN2)2Hung relatedGrondard C; Biondi O; Armand AS; Lecolle S; Della Gaspera B; Pariset C; Li H; Gallien CL; Vidal PP; Chanoine C; Charbonnier F. 2005. Regular exercise prolongs survival in a type 2 spinal muscular atrophy model mouse. J Neurosci 25(33):7615-22. [PubMed: 16107648] [MGI Ref ID J:101180]
Monani UR; Sendtner M; Coovert DD; Parsons DW; Andreassi C; Le TT; Jablonka S; Schrank B; Rossol W; Prior TW; Morris GE; Burghes AH. 2000. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 9(3):333-9. [PubMed: 10655541] [MGI Ref ID J:60592]
Tsai LK; Tsai MS; Lin TB; Hwu WL; Li H. 2006. Establishing a standardized therapeutic testing protocol for spinal muscular atrophy. Neurobiol Dis 24(2):286-95. [PubMed: 16952456] [MGI Ref ID J:114536]
Tsai MS; Chiu YT; Wang SH; Hsieh-Li HM; Li H. 2006. Abolishing Trp53-dependent apoptosis does not benefit spinal muscular atrophy model mice. Eur J Hum Genet 14(3):372-5. [PubMed: 16391561] [MGI Ref ID J:129232]
Chang JG; Hsieh-Li HM; Jong YJ; Wang NM; Tsai CH; Li H. 2001. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A 98(17):9808-13. [PubMed: 11504946] [MGI Ref ID J:94612]Tsai LK; Tsai MS; Lin TB; Hwu WL; Li H. 2006. Establishing a standardized therapeutic testing protocol for spinal muscular atrophy. Neurobiol Dis 24(2):286-95. [PubMed: 16952456] [MGI Ref ID J:114536]
Tsai MS; Chiu YT; Wang SH; Hsieh-Li HM; Li H. 2006. Abolishing Trp53-dependent apoptosis does not benefit spinal muscular atrophy model mice. Eur J Hum Genet 14(3):372-5. [PubMed: 16391561] [MGI Ref ID J:129232]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry The Smn1 (survival motor neuron 1) gene on Chr 13 and the randomly inserted transgene are not linked and will segregate independently. Breeding pairs offered by The Jackson Laboratory will be made up of : (a) One mouse homozygous for the transgene and homozygous for the targeted Smn1 mutation.
(b) One mouse with no transgene and heterozygous for the targeted Smn1 mutation.The mouse homozygous for the transgene and homozygous for the targeted Smn1 mutation displays a varied III SMA phenotype, while the mouse with no transgene and heterozygous for the targeted Smn1 mutation is phenotypically normal. Offspring resulting from the mating of breeder pairs can posses the following genotypes:
(1) Hemizygous for the transgene and heterozygous for the targeted mutation (50%)
(2) Hemizygous for the transgene and homozygous for the targeted mutation (50%)Mice that are hemizygous the transgene and heterozygous for the targeted mutation are phenotypically normal. Mice hemizygous for the transgene and homozygous for the targeted mutation display a SMA-like phenotype.
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $229.70 Female or Male Homozygous for Tg(SMN2)2Hung, Heterozygous for Smn1tm1Hung $229.70 Female or Male Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung Individual Mouse Price $229.70 Female or Male Noncarrier, Heterozygous for Smn1tm1Hung *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $459.40 Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung x Noncarrier, Heterozygous for Smn1tm1Hung $459.40 Noncarrier, Heterozygous for Smn1tm1Hung x Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung
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. |
|---|---|
| Supply Notes |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $298.70 Female or Male Homozygous for Tg(SMN2)2Hung, Heterozygous for Smn1tm1Hung $298.70 Female or Male Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung Individual Mouse Price $298.70 Female or Male Noncarrier, Heterozygous for Smn1tm1Hung *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $597.30 Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung x Noncarrier, Heterozygous for Smn1tm1Hung $597.30 Noncarrier, Heterozygous for Smn1tm1Hung x Homozygous for Tg(SMN2)2Hung, Homozygous for Smn1tm1Hung
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. |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| None Available | ||
| Appropriate controls depend on the nature of the experiment. FVB/NJ mice (Stock No. 001800) may be included among the controls considered. | ||
| 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. | ||
General Terms and Conditions
View JAX® Mice & Services Conditions of Use.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by non-profits requires an Material Transger Agreement (MTA) and for-profit entities require a license.
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
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