Overview

Also Known As:Smn^Res , Smn^COIN

While these mutant mice on the mixed B6;129 genetic background are no longer available, mice harboring the same Smn1^{tm3(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 (Smn^Res; 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.

Donating Investigator

Andrew Murphy, Regeneron Pharmaceuticals, Inc.

Genetic overview

Genetic Background	Generation

Smn1^{tm3(SMN2/Smn1)Mrph}

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change)	Smn1	survival motor neuron 1

View Genetics

Research Applications

Developmental Biology Research
Neurobiology Research

View All Research Applications

Details

Detailed Description

The Smn rescue allele (Smn^Res; 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 Smn^Res 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.

Development

Creation of the Smn rescue allele (Smn^Res; 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).

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Murphy A (Regeneron Pharmaceuticals, Inc.). 2008. Smn1 hybrid rescue allele, COIN (conditional inversion) Personal CommunicationMGI: J:135423

View All References

Genetics

Smn1^{tm3(SMN2/Smn1)Mrph}

Allele Symbol: Smn1^{tm3(SMN2/Smn1)Mrph}

Allele Name	targeted mutation 3, Andrew Murphy
Allele Type	Targeted (Conditional ready (e.g. floxed), Humanized sequence, No functional change)
Allele Synonym(s)	hybrid rescue allele; Smn^INV; Smn^Res; 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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Developmental Biology Research
- Embryonic Lethality (Homozygous)
Neurobiology Research
- Spinal Muscular Atrophy (SMA)
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Smn1^{tm3(SMN2/Smn1)Mrph}/Smn1^{tm3(SMN2/Smn1)Mrph}
involves: 129S6/SvEvTac * C57BL/6NTac

mortality/aging

prenatal lethality, complete penetrance
- homozygotes die during development

References

Murphy A (Regeneron Pharmaceuticals, Inc.). 2008. Smn1 hybrid rescue allele, COIN (conditional inversion) Personal CommunicationMGI: J:135423

Additional - Smn1^{tm3(SMN2/Smn1)Mrph} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Smn1
- Separated MCA:Smn1
- Genotyping resources and troubleshooting
Mating System
- +/+ sibling x Heterozygote

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Also Known As:SmnRes , SmnCOIN

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Smn1tm3(SMN2/Smn1)Mrph

Allele Symbol: Smn1tm3(SMN2/Smn1)Mrph

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Smn1tm3(SMN2/Smn1)Mrph/Smn1tm3(SMN2/Smn1)Mrphinvolves: 129S6/SvEvTac * C57BL/6NTac

mortality/aging

References

Additional - Smn1tm3(SMN2/Smn1)Mrph related

Genotyping Protocols

Mating System

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:Smn^Res , Smn^COIN

Smn1^{tm3(SMN2/Smn1)Mrph}

Allele Symbol: Smn1^{tm3(SMN2/Smn1)Mrph}

Genotype: Smn1^{tm3(SMN2/Smn1)Mrph}/Smn1^{tm3(SMN2/Smn1)Mrph}
involves: 129S6/SvEvTac * C57BL/6NTac

Additional - Smn1^{tm3(SMN2/Smn1)Mrph} related