| |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System See Colony Maintenance Species laboratory mouse Generation N6F?+6 (01-DEC-08) Donating Investigator Arthur Burghes, The Ohio State University 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.
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.
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 | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (178 strains)
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
Phenotype
Phenotype Information
Spinal Muscular Atrophy, Type I; SMA1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1 Spinal Muscular Atrophy, Type III; SMA3 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Smn1tm1Msd/Smn1tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Tg(SMN2)89Ahmb/0
involves: 129P2/OlaHsd * FVB/N
- nervous system phenotype
- abnormal action potential (MGI Ref ID J:81238)
- reduced amplitudes in evoked muscle potentials from tibial nerve
- abnormal axon morphology (MGI Ref ID J:81238)
- ventral roots from L1-L5 lumbar spinal cord region contain few myelinated axons
- remaining axons are shriveled and exhibit Wallerian degeneration
- abnormal motor neuron morphology (MGI Ref ID J:81238)
- abnormal motor nerve terminal sprouting (MGI Ref ID J:81238)
- axon sprouting occurs in gastrocnemius and triceps muscles
- sprouts are both nodal and emerge from the neuromuscular junction (terminal)
- decreased motor neuron number (MGI Ref ID J:81238)
- 29% fewer lumbar spinal cord neurons than control in 3.5 month old mice
- 19% fewer facial nucleus neurons than control
- 5 day old mice did not exhibit reduced numbers of motor neurons
- motor neuron degeneration (MGI Ref ID J:81238)
- abnormal neuromuscular synapse morphology (MGI Ref ID J:81238)
- increased number of neuromuscular junctions in gastrocnemius
- neuronal intranuclear inclusions (MGI Ref ID J:81238)
- intranuclear aggregates (gems) of the SMN protein in spinal cord are fewer and less intense than in normal littermates
- muscle phenotype
- abnormal muscle electrophysiology (MGI Ref ID J:81238)
- samples from multiple pelvic and thoracic muscles exhibit abnormal spontaneous activity of single muscle fibers and of motor units in 4-6 month old mice
- abnormal activity is occasionally accompanied by biphasic sharp waves
- muscular atrophy (MGI Ref ID J:81238)
- angulated and atrophic fibers observed in gastrocnemius and to a lesser extent in quadriceps and intercostal muscles
- life span-post-weaning/aging
- premature death (MGI Ref ID J:81238)
- mean survival is 227 days
- growth/size phenotype
- decreased body size (MGI Ref ID J:81238)
- 20-40% smaller than normal littermates
- weight loss (MGI Ref ID J:81238)
- toward the end of life
- reproductive system phenotype
- reduced fertility (MGI Ref ID J:81238)
- behavior/neurological phenotype
- hypoactivity (MGI Ref ID J:81238)
- mice are less active by 3 weeks of age compared to normal littermates
- exhibit very little activity toward the end of life
- limb grasping (MGI Ref ID J:81238)
- muscle weakness exhibited by 3 weeks of age
- poor grooming (MGI Ref ID J:81238)
- mice fail to groom efficiently toward the end of life
- respiratory system phenotype
- hypopnea (MGI Ref ID J:81238)
- mice exhibit short, shallow breeding toward the end of life
Smn1tm1Msd/Smn1tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Tg(SMN2)89Ahmb/Tg(SMN2)89Ahmb
involves: 129P2/OlaHsd * FVB/N
- nervous system phenotype
- abnormal lumbar dorsal root ganglion morphology (MGI Ref ID J:131663)
- at 1 year of age, mice have significantly reduced root counts compared to mice homozygous for Smn1tm1Msd, Tg(Prnp-SMN)92Ahmb, and Tg(SMN2)89Ahmb
- decreased motor neuron number (MGI Ref ID J:131663)
- mice exhibit motor neuron loss
Smn1tm1Msd/Smn1tm1Msd Tg(SMN1*A2G)2023Ahmb/Tg(SMN1*A2G)2023Ahmb Tg(SMN2)89Ahmb/?
involves: 129P2/OlaHsd * FVB/N
- nervous system phenotype
- abnormal motor nerve terminal sprouting (MGI Ref ID J:81238)
- axon sprouting occurs in gastrocnemius and triceps muscles
- sprouts are both nodal and emerge from the neuromuscular junction (terminal)
- otherwise, phenotype is indistinguishable from littermates
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)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Smn1tm1Msd | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Michael Sendtner | ||
| Allele Type | Targeted (Reporter) | ||
| 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 | ||
| Allele Type | Transgenic (random, expressed) | ||
| 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 | ||
| Allele Type | Transgenic (random, expressed) | ||
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Smn1tm1Msd, MCA, vers. 3
Smn1tm1Msd, STD PCR, vers. 2
Tg(SMN1*A2G)2023Ahmb, , vers. 1
Tg(SMN2)89Ahmb, STD PCR, vers. 3
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Monani 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]
Additional References
Smn1tm1Msd relatedTg(SMN1*A2G)2023Ahmb relatedButchbach ME; Edwards JD; Burghes AH. 2007. Abnormal motor phenotype in the SMNDelta7 mouse model of spinal muscular atrophy. Neurobiol Dis 27(2):207-19. [PubMed: 17561409] [MGI Ref ID J:134824]
El-Khodor BF; Edgar N; Chen A; Winberg ML; Joyce C; Brunner D; Suarez-Farinas M; Heyes MP. 2008. Identification of a battery of tests for drug candidate evaluation in the SMNDelta7 neonate model of spinal muscular atrophy. Exp Neurol 212(1):29-43. [PubMed: 18455159] [MGI Ref ID J:137949]
Gavrilina 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]
Jablonka S; Beck M; Lechner BD; Mayer C; Sendtner M. 2007. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy. J Cell Biol 179(1):139-49. [PubMed: 17923533] [MGI Ref ID J:134807]
Jablonka S; Holtmann B; Meister G; Bandilla M; Rossoll W; Fischer U; Sendtner M. 2002. Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death. Proc Natl Acad Sci U S A 99(15):10126-31. [PubMed: 12091709] [MGI Ref ID J:81784]
Jablonka S; Karle K; Sandner B; Andreassi C; von Au K; Sendtner M. 2006. Distinct and overlapping alterations in motor and sensory neurons in a mouse model of spinal muscular atrophy. Hum Mol Genet 15(3):511-8. [PubMed: 16396995] [MGI Ref ID J:105422]
Jablonka S; Schrank B; Kralewski M; Rossoll W; Sendtner M. 2000. Reduced survival motor neuron (Smn) gene dose in mice leads to motor neuron degeneration: an animal model for spinal muscular atrophy type III. Hum Mol Genet 9(3):341-6. [PubMed: 10655542] [MGI Ref ID J:60591]
Kariya S; Park GH; Maeno-Hikichi Y; Leykekhman O; Lutz C; Arkovitz MS; Landmesser LT; Monani UR. 2008. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17(16):2552-69. [PubMed: 18492800] [MGI Ref ID J:138437]
Le 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]
McGovern VL; Gavrilina TO; Beattie CE; Burghes AH. 2008. Embryonic motor axon development in the severe SMA mouse. Hum Mol Genet 17(18):2900-9. [PubMed: 18603534] [MGI Ref ID J:138317]
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]
Murray LM; Comley LH; Thomson D; Parkinson N; Talbot K; Gillingwater TH. 2008. Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet 17(7):949-62. [PubMed: 18065780] [MGI Ref ID J:132467]
Novoyatleva T; Heinrich B; Tang Y; Benderska N; Butchbach ME; Lorson CL; Lorson MA; Ben-Dov C; Fehlbaum P; Bracco L; Burghes AH; Bollen M; Stamm S. 2008. Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing. Hum Mol Genet 17(1):52-70. [PubMed: 17913700] [MGI Ref ID J:130114]
Rose FF Jr; Meehan PW; Coady TH; Garcia VB; Garcia ML; Lorson CL. 2008. The Wallerian degeneration slow (Wld(s)) gene does not attenuate disease in a mouse model of spinal muscular atrophy. Biochem Biophys Res Commun 375(1):119-23. [PubMed: 18680723] [MGI Ref ID J:140130]
Rossoll W; Jablonka S; Andreassi C; Kroning AK; Karle K; Monani UR; Sendtner M. 2003. Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol 163(4):801-12. [PubMed: 14623865] [MGI Ref ID J:86712]
Schrank B; Gotz R; Gunnersen JM; Ure JM; Toyka KV; Smith AG ; Sendtner M. 1997. Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci U S A 94(18):9920-5. [PubMed: 9275227] [MGI Ref ID J:42813]
Walker MP; Rajendra TK; Saieva L; Fuentes JL; Pellizzoni L; Matera AG. 2008. SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet 17(21):3399-410. [PubMed: 18689355] [MGI Ref ID J:140332]
Tg(SMN2)89Ahmb relatedAvila AM; Burnett BG; Taye AA; Gabanella F; Knight MA; Hartenstein P; Cizman Z; Di Prospero NA; Pellizzoni L; Fischbeck KH; Sumner CJ. 2007. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117(3):659-71. [PubMed: 17318264] [MGI Ref ID J:120738]
Gavrilina 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]
Avila AM; Burnett BG; Taye AA; Gabanella F; Knight MA; Hartenstein P; Cizman Z; Di Prospero NA; Pellizzoni L; Fischbeck KH; Sumner CJ. 2007. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 117(3):659-71. [PubMed: 17318264] [MGI Ref ID J:120738]
Butchbach ME; Edwards JD; Burghes AH. 2007. Abnormal motor phenotype in the SMNDelta7 mouse model of spinal muscular atrophy. Neurobiol Dis 27(2):207-19. [PubMed: 17561409] [MGI Ref ID J:134824]
Gavrilina 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]
Jablonka S; Beck M; Lechner BD; Mayer C; Sendtner M. 2007. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy. J Cell Biol 179(1):139-49. [PubMed: 17923533] [MGI Ref ID J:134807]
Jablonka S; Karle K; Sandner B; Andreassi C; von Au K; Sendtner M. 2006. Distinct and overlapping alterations in motor and sensory neurons in a mouse model of spinal muscular atrophy. Hum Mol Genet 15(3):511-8. [PubMed: 16396995] [MGI Ref ID J:105422]
Kariya S; Park GH; Maeno-Hikichi Y; Leykekhman O; Lutz C; Arkovitz MS; Landmesser LT; Monani UR. 2008. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17(16):2552-69. [PubMed: 18492800] [MGI Ref ID J:138437]
Le 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]
McGovern VL; Gavrilina TO; Beattie CE; Burghes AH. 2008. Embryonic motor axon development in the severe SMA mouse. Hum Mol Genet 17(18):2900-9. [PubMed: 18603534] [MGI Ref ID J:138317]
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]
Murray LM; Comley LH; Thomson D; Parkinson N; Talbot K; Gillingwater TH. 2008. Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum Mol Genet 17(7):949-62. [PubMed: 18065780] [MGI Ref ID J:132467]
Novoyatleva T; Heinrich B; Tang Y; Benderska N; Butchbach ME; Lorson CL; Lorson MA; Ben-Dov C; Fehlbaum P; Bracco L; Burghes AH; Bollen M; Stamm S. 2008. Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing. Hum Mol Genet 17(1):52-70. [PubMed: 17913700] [MGI Ref ID J:130114]
Rossoll W; Jablonka S; Andreassi C; Kroning AK; Karle K; Monani UR; Sendtner M. 2003. Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol 163(4):801-12. [PubMed: 14623865] [MGI Ref ID J:86712]
Walker MP; Rajendra TK; Saieva L; Fuentes JL; Pellizzoni L; Matera AG. 2008. SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain. Hum Mol Genet 17(21):3399-410. [PubMed: 18689355] [MGI Ref ID J:140332]
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 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.
Mating System See above Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $229.70 Female or Male Homozygous for Tg(SMN2)89Ahmb, Hemizygous for Tg(SMN1*A2G)2023Ahmb, Homozygous for Smn1tm1Msd *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $239.80 Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd $239.80 Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Heterozygous for Smn1tm1Msd $239.80 Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Homozygous for Smn1tm1Msd
Additional Supply Details
| Supply Notes |
|
|---|
| Pricing for International shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $298.70 Female or Male Homozygous for Tg(SMN2)89Ahmb, Hemizygous for Tg(SMN1*A2G)2023Ahmb, Homozygous for Smn1tm1Msd *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.80 Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd $311.80 Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Heterozygous for Smn1tm1Msd $311.80 Homozygous for Tg(SMN2)89Ahmb, Noncarrier, Heterozygous for Smn1tm1Msd x Homozygous for Tg(SMN2)89Ahmb, Homozygous for Tg(SMN1*A2G)2023Ahmb, Homozygous for Smn1tm1Msd
Additional Supply Details
| Supply Notes |
|
|---|
|
|
|
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 | ||
|---|---|---|
| 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 | ||
| 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
See Terms of Use
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: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
Contact information
General inquiries
Contracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice & Services Conditions of Use
“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. THE LABORATORY 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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.
No Liability
In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.
MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.