This triple mutant mouse strain harbors two human SMN2 transgenic alleles and a single Smn1 targeted mutation, and may be useful in studies of Spinal Muscular Atrophy.
IMR Colony, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type |
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Transgenic (Hypomorph, Inserted expressed sequence, Humanized sequence) |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change) | Smn1 | survival motor neuron 1 |
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.
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.
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
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Site of Expression | Grm7Tg(SMN2)89Ahmb |
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
Site of Expression | Tg(SMN2*delta7)4299Ahmb |
Site of Expression | 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 and the resulting SMN protein is produced in motor neurons. |
Allele Name | transgene insertion 89, Arthur H M Burghes |
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Allele Type | Transgenic (Hypomorph, Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | SMN2; Tg(SMN2)89Ahmb |
Gene Symbol and Name | Grm7, glutamate receptor, metabotropic 7 |
Gene Synonym(s) | |
Promoter | SMN2, survival of motor neuron 2, centromeric, human |
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
Site of Expression | Grm7Tg(SMN2)89Ahmb |
Strain of Origin | FVB/N |
Chromosome | 6 |
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 integrated into intron 4 of the gene. RT-PCR confirmed reduced expression of the gene the transgene is integrated into. |
Mutations Made By | Arthur Burghes, The Ohio State University |
Allele Name | transgene insertion 4299, Arthur H M Burghes |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | SMNdelta7; Tg(SMN1*delta7)4299Ahmb |
Gene Symbol and Name | Tg(SMN2*delta7)4299Ahmb, transgene insertion 4299, Arthur H M Burghes |
Gene Synonym(s) | |
Promoter | SMN2, survival of motor neuron 2, centromeric, human |
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
Site of Expression | Tg(SMN2*delta7)4299Ahmb |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | The transgene contains a human SMN2 promoter and a human SMN2 cDNA (SMNdelta7) that lacks exon 7. There are 14 copies of this allele integrated into the genome. |
Mutations Made By | Arthur Burghes, The Ohio State University |
Allele Name | targeted mutation 3, Andrew Murphy |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change) |
Allele Synonym(s) | hybrid rescue allele; SmnINV; SmnRes; Smn1 COIN (conditional inversion) |
Gene Symbol and Name | Smn1, survival motor neuron 1 |
Gene Synonym(s) | |
Site of Expression | 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 and the resulting SMN protein is produced in motor neurons. |
Strain of Origin | (129S6/SvEvTac x C57BL/6NTac)F1 |
Chromosome | 13 |
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. |
Mutations Made By | Nicole Graiff, Regeneron |
When maintaining a live colony, mice heterozygous for Smn1tm3(SMN2/Smn1)Mrph, homozygous for Tg(SMN2*delta7)4299Ahmb and homozygous for Tg(SMN2)89Ahmb may be bred together.
When using the SMNΔ7;SMN2;SmnRes , SMNΔ7;SMN2;SmnCOIN , Moderate Type II SMA Rescue , Delta 7 mouse with hybrid rescue allele mouse strain in a publication, please cite the originating article(s) and include JAX stock #007951 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Smn1<tm3(SMN2/Smn1)Mrph>, Homozygous for Tg(SMN2*delta7)4299Ahmb, Homozygous for Tg(SMN2)89Ahmb/J |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm3(SMN2/Smn1)Mrph> Tg(SMN2* | $2595.00 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm3(SMN2/Smn1)Mrph> Tg(SMN2* | $2595.00 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm3(SMN2/Smn1)Mrph> Tg(SMN2* | $3373.50 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm3(SMN2/Smn1)Mrph> Tg(SMN2* | $3373.50 |
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