While these mutant mice on the mixed B6;129 genetic background are no longer available, mice harboring the same Smn1tm3(SMN2/Smn1)Mrph allele are available on an FVB congenic background (Stock No. 007964) and a C57BL/6 congenic background (Stock No. 007966). The Smn rescue allele (SmnRes; also called Smn1 conditional inversion or Smn1 COIN) allele is a functional null in the non-recombined state. As such, homozygous animals are embryonic lethal. This 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.
Andrew Murphy, Regeneron Pharmaceuticals, Inc.
Genetic Background | Generation |
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|
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 |
The Smn rescue allele (SmnRes; also called Smn1 conditional inversion or Smn1 COIN) is a functional null in the non-recombined state. As such, homozygous animals are embryonic lethal. Prior to Cre recombination, no full-length SMN transcript is detected in somatic tissue by RT-PCR. No spontaneous inversion of the allele is reported in the absence of Cre recombinase. The SmnRes allele is designed to revert to a fully functional SMN upon exposure to Cre recombinase. Specifically, Cre recombinase irreversibly inverts the fragment bordered by the lox71 and lox66 sites, and the resulting allele is "rescued" into a format that contains mouse Smn1 exons 1-7 and human SMN2 exon 8. Because the mouse Smn1 exon 8 is efficiently spliced, the majority of the mRNA from the Cre recombinase-induced rescue allele contains mouse Smn1 exon 7. 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.
Creation of the Smn rescue allele (SmnRes; also called Smn1 conditional inversion or Smn1 COIN) allele is described below. 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. 129S6/SvEvTac and C57BL/6Tac derived F1H4 ES cells were used. This strain was maintained on a B6;129 genetic background. This allele is also being backcrossed to both an FVB/NJ genetic background (Stock No. 007964) and C57BL/6J genetic background (Stock No. 007966).
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 |
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