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| These SMN2; Smn; HSA69-SMN mice may be useful for neuromuscular studies including spinal muscular atrophy (SMA). | |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
Description
Strain Information
Type Congenic; Targeted Mutation; Transgenic; Mating System See Colony Maintenance Species laboratory mouse Donating Investigator Arthur Burghes, The Ohio State University Description
As described for SMA mice (see Stock No. 005024), mice homozygous for Smn1tm1Msd targeted mutation (Smn null allele) and human SMN2 low copy line 89 transgene 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 HSA-SMN transgene; with the human alpha-skeletal actin (HSA or ACTA1) promoter directing full-length human SMN expression at high levels in skeletal muscle. When the HSA-SMN transgene is derived from HSA69-SMN founder mice, skeletal muscle-specific SMN expression is preserved, and homozygous SMN2; Smn; HSA69-SMN mutant animals (Stock No. 008209) have the same phenotype as homozygous SMA mice. In contrast, expression of the HSA-SMN transgene derived from HSA63-SMN founder mice is leaky; with high SMN expression in heart and low SMN expression in spinal cord, brain, and liver. This additional SMN expression in neural cells rescues homozygous SMN2; Smn; HSA63-SMN mice (Stock No. 008203) from the severe SMA phenotype and significantly increases lifespan (average 160 days). Homozygous SMN2; Smn; HSA63-SMN mice also exhibit necrotic tail development with loss of the tail giving them a "hamster" appearance. These SMN2; Smn; HSA69-SMN mice may be useful for neuromuscular studies including spinal muscular atrophy (SMA).Development
These SMN2; Smn; HSA69-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 HSA-SMN transgene was designed with the human alpha-skeletal actin (HSA or ACTA1) promoter region, splice acceptor site from the SV40 VP1 intron, full-length humsn SMN cDNA (containing exons 1-8), and two SV40 polyA signals. This transgene was microinjected into fertilized FVB/N oocytes. Mice from founder line 69 (HSA69-SMN) were found to have 11 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).
To generate the SMN2; Smn; HSA69-SMN mutant strain, FVB/N SMA carrier mice (heterozygous for the Smn1tm1Msd targeted mutation and homozygous for the SMN2 low copy line 89 transgene and backcrossed to FVB/N for at least 5 generations) were bred with FVB/N HSA69-SMN mice. Mice heterozygous for the targeted mutation, heterozygous for the HSA69-SMN transgene, and homozygous for the SMN2 low copy line 89 transgene were maintained for many generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (174 strains)
008203 FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)63Ahmb Tg(SMN2)89Ahmb/J 005026 FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J 008212 STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
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.
Smn1tm1Msd/Smn1tm1Msd Tg(ACTA1-SMN)69Ahmb/Tg(ACTA1-SMN)69Ahmb Tg(SMN2)89Ahmb/Tg(SMN2)89Ahmb
involves: 129P2/OlaHsd * FVB/N
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:131663)
- mice survive an average of 3.5 days, not significantly different from mean lifespan of 4.6 days of Smn1tm1Msd homozygotes
Research Applications
This mouse can be used to support research in many areas including:
Smn1tm1Msd relatedDevelopmental Biology Research
Neurodevelopmental Defects
Perinatal Lethality
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)
Genes & Alleles
Gene & Allele Information
| 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(ACTA1-SMN)69Ahmb | ||
| Allele Name | transgene insertion 69, Arthur H M Burghes | ||
| Common Name(s) | HSA69-SMN; | ||
| 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 | ACTA1, actin, alpha 1, skeletal muscle, human | ||
| Molecular Note | The HSA-SMN transgene was designed with the human alpha-skeletal actin (HSA or ACTA1) promoter region, splice acceptor site from the SV40 VP1 intron, full-length humsn SMN cDNA (containing exons 1-8), and two SV40 polyA signals. Mice from founder line 69(HSA69-SMN) were found to have 11 copies of the transgene. [MGI Ref ID J:131663] [MGI Ref ID J:97103] | ||
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Smn1tm1Msd, STD PCR, vers. 2
Tg(SMN2)89Ahmb, STD PCR, vers. 3
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
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]
Additional References
Smn1tm1Msd related
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]Tg(ACTA1-SMN)69Ahmb relatedEl-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]
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; 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]
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]
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]
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]Tg(SMN2)89Ahmb related
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]
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; 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]
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]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, mice heterozygous for the Smn1tm1Msd targeted mutation, homozygous for the SMN2 (line 89) transgene, and homozygous for the HSA69-SMN transgene may be bred together. The SMN2 (line 89) transgene is reported to have a single copy (thus homozygotes have 2 copies). The HSA69-SMN transgene copy number should be monitored as the phenotype of SMA models may be greatly affected by copy number variations. Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
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.
View All Strains Under Development
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| 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 companies or for-profit entities requires a license prior to shipping.
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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