The Smn1C hybrid allele contains two tandem Smn1/SMN2 genes. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy. In addition to motor deficits, SMN deficiencies in these mice may also be useful as a potential model of chronic pain.
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IMR Colony, The Jackson Laboratory
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Inserted expressed sequence, Humanized sequence) | Smn1 | survival motor neuron 1 |
The hybrid allele in this strain, Smn allele C, contains two tandem Smn1/SMN2 genes. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes. Western blot analysis of full-length SMN in the spinal cord and liver extracts of homozygous mice (Smn1C/C) shows reduced relative SMN total protein (mouse + human) compared with heterozygous and wildtype animals. SMN protein levels are significantly reduced in the spinal cord and liver of homozygoyes. Smn1C/C mice exhibit a mild SMA phenotype due to the preferential splicing of the Δ7-SMN gene product over the full-length SMN product. The homozygous phenotype includes reduced body weight, peripheral necrosis (beginning with the tail and moving toward the hindlimbs and then to the pinnae of the ears), mild progressive neuromuscular junction abnormalities and electrophysiological defects, diminished open field activity, decreased bone mineral density, evidence of cardiac abnormalities and heightened nocioceptive responses. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy.
Development of this model was supported by the Spinal Muscular Atrophy Foundation.
This mutant mouse carries the Smn allele C, which contains two tandem Smn1/SMN2 genes. The first is a hybrid gene in which a 2.2 kbp segment of mouse genome containing exons 7 and 8 of the mouse Smn1 gene was replaced with a 1.3 kbp fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 gene. The second is a full 42 kbp copy of the human SMN2 gene. A selection cassette located downstream from the human SMN2 polyadenylation signal was removed by FLPe expression in ES cells leaving a FRT site at the downstream junction between human and mouse DNA. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes. The (129S6/SvEvTac x C57BL/6NTac)F1 hybrid derived ES cell line F1H4 was used. The mice were crossed to C57BL/6J once, and then were backcrossed to FVB/NJ using a speed congenic protocol.
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
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Expressed Gene | Smn1, survival motor neuron 1, mouse, laboratory |
Site of Expression | Smn1 is normally expressed in motor neurons, particularly in the spinal chord. |
Allele Name | targeted mutation 5, Andrew Murphy |
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Allele Type | Targeted (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | Smn allele C |
Gene Symbol and Name | Smn1, survival motor neuron 1 |
Gene Synonym(s) | |
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
Expressed Gene | Smn1, survival motor neuron 1, mouse, laboratory |
Site of Expression | Smn1 is normally expressed in motor neurons, particularly in the spinal chord. |
Strain of Origin | (129S6/SvEvTac x C57BL/6NTac)F1 |
Chromosome | 13 |
Molecular Note | The allele encodes two coding sequences: the first is a hybrid gene in which a 2.2 kb segment of mouse genome containing exons 7 and 8 of the mouse Smn1 gene was replaced with a 1.3 kb fragment of human genomic DNA containing exons 7 and 8 of the human SMN2 gene and the second is a full 42 kb copy of the human SMN2 gene. A selection cassette located downstream from the human SMN2 polyadenylation signal was removed by FLPe expression in ES cells leaving a FRT site at the downstream junction between human and mouse DNA. Because exon 7 is derived from human SMN2, it is skipped in approximately 90% of the processed mRNA derived from both genes. 2 independent clones for this allele were generated and clone A2 was used to generated mice. |
Mutations Made By | Andrew Murphy, Regeneron Pharmaceuticals, Inc. |
When maintaining a live colony, these mice can be bred as heterozygotes.
When using the Smn1C mouse strain in a publication, please cite the originating article(s) and include JAX stock #008604 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Smn1<tm5(Smn1/SMN2)Mrph> |
Frozen Mouse Embryo | FVB.129(B6)-Smn1<tm5(Smn1/SMN2)Mrph>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129(B6)-Smn1<tm5(Smn1/SMN2)Mrph>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB.129(B6)-Smn1<tm5(Smn1/SMN2)Mrph>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB.129(B6)-Smn1<tm5(Smn1/SMN2)Mrph>/J Frozen Embryo | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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