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| This triple mutant mouse harbors two transgenic alleles and a single targeted mutation. The Tg(SMN2*delta7)4299Ahmb allele consists of a human SMN2 (survival of motor neuron 2, centromeric) cDNA lacking exon 7 whereas the Tg(SMN2)89Ahmb allele consists of the entire human SMN2 gene. The targeted mutant Smn1tm3(SMN2/Smn1/SMN2)Mrph allele is engineered to revert to a fully functional Smn1 allele upon Cre-mediated recombination. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy. | |||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Former Names STOCK Smn1tm1Msd Smn1tm3(SMN2/Smn1/SMN2)Mrph Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb/J (Changed: 18-JUN-08 ) Type Mutant Stock; Targeted Mutation; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator IMR Colony, The Jackson Laboratory Description
This triple mutant mouse harbors two transgenic alleles and a single targeted mutation. The Tg(SMN2*delta7)4299Ahmb allele consists of a human SMN2 (survival of motor neuron 2, centromeric) 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 Smn1tm3(SMN2/Smn1/SMN2)Mrph allele and homozygous for the two transgenic alleles should function similarly to SMA mutant strain FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J (Stock no. 005025 ). The targeted mutant Smn1tm3(SMN2/Smn1/SMN2)Mrph allele is engineered to revert to a fully functional Smn1 allele upon Cre-mediated recombination. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy.Importation of this model was supported by the Spinal Muscular Atrophy Foundation.
Development
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 (survival of motor neuron 2, centromeric) 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. These double mutants were in turn mated with mice bearing the Smn1tm3(SMN2/Smn1/SMN2)Mrph targeted mutation. The 129S6/SvEvTac X C57BL/6Tac hybrid derived F1H4 ES cell line was used to generate the targeted mutation.
Related Strains
Strains carrying Smn1tm3(SMN2/Smn1)Mrph allele
007249 B6;129-Smn1tm3(SMN2/Smn1)Mrph/J View Strains carrying Smn1tm3(SMN2/Smn1)Mrph (1 strain)
005025 FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J
008206 FVB.Cg-Smn1tm1Msd Tg(SMN2)566Ahmb/J 005058 FVB.Cg-Tg(SMN2)2Hung Smn1tm1Hung/J
Phenotype
Phenotype Information
This mouse can be used to support research in many areas including:
Neurobiology Research
Neurodegeneration
Spinal Muscular Atrophy (SMA)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Smn1tm3(SMN2/Smn1)Mrph | ||
|---|---|---|---|
| Allele Name | targeted mutation 3, Andrew Murphy | ||
| Allele Type | Targeted (Floxed/Frt) | ||
| Common Name(s) | Smn1 COIN (conditional inversion); | ||
| Strain of Origin | (129 x C57BL/6)F1 | ||
| ES Cell Line Name | F1H4 | ||
| ES Cell Line Strain | (129 x C57BL/6)F1 | ||
| 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 | Exons 7 and 8 of the mouse Smn1 (survival motor neuron 1) gene and a several hundred base pairs of flanking sequence were replaced with a fragment containing, in order: 1) an inverted lox71 site; 2) exon 7 from the human SMN2 (survival of motor neuron 2,centromeric) gene flanked by several hundred base pairs of intron sequence; 3) an inverted copy of mouse Smn1 exon 7 flanked by several hundred base pairs of intron sequence; 4) a lox66 site; 5) an FRT site remnant from a deleted selection cassette; and 6) human SMN2 exon 8 including the 3'UTR and polyA signal with several hundred base pairs of flanking sequence. The engineered allele expresses a hybrid Smn1 gene containing mouse Smn1 exons 1 through 6 and human SMN2 exons 7 and 8. The human SMN2 exon 7 is skipped in the majority of mRNA derived from the hybrid gene due to a single base pair difference in human SMN2 exon 7, compared to human SMN1 exon 7. Following Cre-mediated irreversible inversion of the fragment bordered by the lox71 and lox66 sites, the allele is "rescued" into a format that contains mouse Smn1 exons 1 through 7 and human SMN2 exon 8. Because the mouse Smn1 exon 8 is efficiently spliced, the majority of the mRNA from the rescue allele after Cre-mediated inversion contains mouse Smn1 exon 7. [MGI Ref ID J:135423] | ||
| 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] | ||
| Allele Symbol | Tg(SMN2*delta7)4299Ahmb | ||
| Allele Name | transgene insertion 4299, Arthur H M Burghes | ||
| Allele Type | Transgenic (random, expressed) | ||
| 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Smn1tm1Msd, MCA, vers. 3
Smn1tm1Msd, STD PCR, vers. 2
Smn1tm3(SMN2/Smn1)Mrph, MCA, vers. 2
Smn1tm3(SMN2/Smn1)Mrph, SEP PCR, vers. 1
Tg(SMN2)89Ahmb, STD PCR, vers. 3
Tg(SMN2*delta7)4299Ahmb, QPCR, vers. 3
Tg(SMN2*delta7)4299Ahmb, STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
References
References
Additional References
Smn1tm3(SMN2/Smn1)Mrph relatedTg(SMN2)89Ahmb relatedMurphy A (Regeneron Pharmaceuticals, Inc.). 2008. Smn1 hybrid rescue allele, COIN (conditional inversion) Personal Communication :. [MGI Ref ID J:135423]
Tg(SMN2*delta7)4299Ahmb 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]
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; 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]
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]
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]
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]
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]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
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