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| The hybrid allele in this strain, Smn allele C, contains two tandem Smn1/SMN2 genes. Further characterization is currently in progress. This mutant mouse strain may be useful in studies of Spinal Muscular Atrophy. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Heterozygote (Female x Male) 05-MAR-12 Species laboratory mouse Generation N8 (25-MAR-11)
Generation DefinitionsDonating Investigator IMR Colony, The Jackson Laboratory Description
The hybrid allele in this strain, Smn allele C, contains two tandem Smn1/SMN2 genes. Further characterization is currently in progress. 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.
Development
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 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. 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. The 129S6/SvEvTac X C57BL/6Tac 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.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Spinal Muscular Atrophy (SMA) Models
View Spinal Muscular Atrophy (SMA) Models (49 strains)
008714 B6.129-Smn1tm5(Smn1/SMN2)Mrph/J 008384 B6;129-Smn1tm5(Smn1/SMN2)Mrph/J
Additional Web Information
Reference Guide to Mouse Models of Spinal Muscular Atrophy manual [.pdf]
Visit the Spinal Muscular Atrophy (SMA) Mouse Model Resource site for helpful information on SMA Disease and research resources.
Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Spinal Muscular Atrophy, Type II; SMA2
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Spinal Muscular Atrophy, Type III; SMA3 (SMN1)
Spinal Muscular Atrophy, Type IV; SMA4 (SMN1)
assigned by genotype
Smn1tm5(Smn1/SMN2)Mrph/Smn1tm5(Smn1/SMN2)Mrph
FVB.129(B6)-Smn1tm5(Smn1/SMN2)Mrph/J
- skeleton phenotype
- decreased bone mineral content
- 6 month old mutants exhibit lower bone mineral content (MGI Ref ID J:186987)
- decreased bone mineral density
- 6 month old mutants exhibit lower bone mineral density (MGI Ref ID J:186987)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Smn1tm5(Smn1/SMN2)Mrph/Smn1+
involves: 129S6/SvEvTac * C57BL/6NTac
- no phenotypic analysis
- *normal* no phenotypic analysis
- no phenotypic analysis available (MGI Ref ID J:135425)
Smn1tm5(Smn1/SMN2)Mrph/Smn1tm5(Smn1/SMN2)Mrph
involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac
- growth/size phenotype
- decreased body size
- by P15 and P20, males and females, respectively, are smaller than wild-type controls (MGI Ref ID J:186987)
- cellular phenotype
- necrosis
- mutants present with progressive necrosis of peripheral body parts beginning with the tail and moving toward the hindlimbs and then to the pinnae of the ears (MGI Ref ID J:186987)
- onset of tail necrosis is seen as early as P5 and progresses to complete loss of the tail by 45 days of age (MGI Ref ID J:186987)
- tail necrosis at 20-40 days of age is characterized by disorganization of muscle fiber bundles along with loss of intact vasculature in the absence of an inflammatory lesion as mice age (MGI Ref ID J:186987)
- muscle phenotype
- decreased skeletal muscle fiber size (MGI Ref ID J:186987)
- behavior/neurological phenotype
- enhanced coordination
- hyperalgesia (MGI Ref ID J:186987)
- decreased thermal nociceptive threshold
- 6-8 week old mutants (with no paw necrosis) exhibit an increase in sensitivity to moderately noxious heat with a significant decrease in hindpaw withdrawal latencies when placed on a 45C and 48C metal plate, however no differences in response to high noxious stimulus of 52C is seen (MGI Ref ID J:186987)
- 6-8 week old mutants exhibit robust sensitization in the evaporative cooling assay, responding more vigorously than controls, indicating increased sensitivity to temperature (MGI Ref ID J:186987)
- hyperresponsive to tactile stimuli
- in plantar von Frey testing, 6-8, 20 and 24 week old mutants show significantly lower paw withdrawal force than controls, indicating hyperalgesia (MGI Ref ID J:186987)
- cardiovascular system phenotype
- abnormal blood vessel morphology
- thermal imaging indicates that vascular destruction in the tail occurs before overt exterior necrosis (MGI Ref ID J:186987)
- lateral vasculature of the tail is primarily affected, with a loss of integrity in the vessel wall (most evident in the inner tunica intima of the small lateral vasculature) whereas the ventral artery remains intact until the very last stages of necrosis (MGI Ref ID J:186987)
- decreased heart rate
- integument phenotype
- hyperalgesia (MGI Ref ID J:186987)
- decreased thermal nociceptive threshold
- 6-8 week old mutants (with no paw necrosis) exhibit an increase in sensitivity to moderately noxious heat with a significant decrease in hindpaw withdrawal latencies when placed on a 45C and 48C metal plate, however no differences in response to high noxious stimulus of 52C is seen (MGI Ref ID J:186987)
- 6-8 week old mutants exhibit robust sensitization in the evaporative cooling assay, responding more vigorously than controls, indicating increased sensitivity to temperature (MGI Ref ID J:186987)
- hyperresponsive to tactile stimuli
- in plantar von Frey testing, 6-8, 20 and 24 week old mutants show significantly lower paw withdrawal force than controls, indicating hyperalgesia (MGI Ref ID J:186987)
- nervous system phenotype
- abnormal neuromuscular synapse morphology
- at P90, about 10% of neuromuscular junctions (NMJs) in splenius, longissimus, and semispinalis muscles show abnormal morphology, with fragmented acetylcholine receptor clusters, abnormal thin nerve terminals, some junctions innervated by multiple nerve terminals, and nerve terminal sprouting, indicating that synaptic maintenance is mildly disrupted (MGI Ref ID J:186987)
- however, at P8 and P14, all NJMs are innervated and no nerve sprouting is seen, indicating that synapse formation at the NJM is not affected in mutants (MGI Ref ID J:186987)
- abnormal synaptic transmission
- abnormal endplate potential
- abnormal miniature endplate potential
- at P90 and P350, muscle exhibits a slight increase in the spontaneous miniature endplate potential (MEPP) amplitude (MGI Ref ID J:186987)
- upon nerve stimulation, the quantal content is decreased by 13-14% in both mutants at P90 and P350 (MGI Ref ID J:186987)
- however, no difference from controls is seen in the MEPP frequency or the evoked endplate potential (EPP) amplitudes (MGI Ref ID J:186987)
Smn1tm5(Smn1/SMN2)Mrph/Smn1tm5(Smn1/SMN2)Mrph
B6.129-Smn1tm5(Smn1/SMN2)Mrph/JThis mouse can be used to support research in many areas including:
Neurobiology Research
Spinal Muscular Atrophy (SMA)
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Smn1tm5(Smn1/SMN2)Mrph | ||
|---|---|---|---|
| Allele Name | targeted mutation 5, Andrew Murphy | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Smn allele C; | ||
| Mutation Made By | Andrew Murphy, Regeneron Pharmaceuticals, Inc. | ||
| Strain of Origin | (129S6/SvEvTac x C57BL/6NTac)F1 | ||
| ES Cell Line Name | F1H4 | ||
| ES Cell Line Strain | (129S6/SvEvTac x C57BL/6NTac)F1 | ||
| Expressed Gene | Smn1, survival motor neuron 1, mouse, laboratory | ||
| Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human | ||
| 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. [MGI Ref ID J:135425] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Generic LacZ Melt Curve Analysis, Melt Curve Analysis
Tg(SMN2*delta7)4299Ahmb, QPCR
Smn1tm5(Smn1/SMN2)Mrph, Melt Curve Analysis
Smn1tm5(Smn1/SMN2)Mrph, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Osborne M; Gomez D; Feng Z; McEwen C; Beltran J; Cirillo K; El-Khodor B; Lin MY; Li Y; Knowlton WM; McKemy DD; Bogdanik L; Butts-Dehm K; Martens K; Davis C; Doty R; Wardwell K; Ghavami A; Kobayashi D; Ko CP; Ramboz S; Lutz C. 2012. Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models. Hum Mol Genet :. [PubMed: 22802075] [MGI Ref ID J:186987]
Additional References
Smn1tm5(Smn1/SMN2)Mrph relatedMurphy A (Regeneron Pharmaceuticals, Inc.). 2008. Smn allele C. Personal Communication :. [MGI Ref ID J:135425]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as heterozygotes. Mating System Homozygote x Heterozygote (Female x Male) 05-MAR-12 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Heterozygous for Smn1tm5(Smn1/SMN2)Mrph $232.00 Female or Male Homozygous for Smn1tm5(Smn1/SMN2)Mrph
Price per Pair (US dollars $) Pair Genotype $464.00 Homozygous for Smn1tm5(Smn1/SMN2)Mrph x Heterozygous for Smn1tm5(Smn1/SMN2)Mrph Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Heterozygous for Smn1tm5(Smn1/SMN2)Mrph $301.60 Female or Male Homozygous for Smn1tm5(Smn1/SMN2)Mrph
Price per Pair (US dollars $) Pair Genotype $603.20 Homozygous for Smn1tm5(Smn1/SMN2)Mrph x Heterozygous for Smn1tm5(Smn1/SMN2)Mrph Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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