Overview

Also Known As:SMNΔ7;SMN2;Smn^Res , SMNΔ7;SMN2;Smn^COIN , Moderate Type II SMA Rescue , Delta 7 mouse with hybrid rescue allele

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.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Grm7^{Tg(SMN2)89Ahmb}

Allele Type
Transgenic (Hypomorph, Inserted expressed sequence, Humanized sequence)

Tg(SMN2*delta7)4299Ahmb

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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

Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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 Smn1^{tm3(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 Smn1^tm1Msd/J (Stock No. 005025). The targeted mutant Smn1^{tm3(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.

Development

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 Smn1^{tm3(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.

Expression Data

Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Site of Expression	Human SMN2 protein is expressed in the tissues examined (brain, liver, spinal cord) [Stock No. 005024].
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.

Control Suggestions

Wild-type male from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Grm7^{Tg(SMN2)89Ahmb}

Allele Symbol: Grm7^{Tg(SMN2)89Ahmb}

Allele Name	transgene insertion 89, Arthur H M Burghes
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	Human SMN2 protein is expressed in the tissues examined (brain, liver, spinal cord) [Stock No. 005024].
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

Tg(SMN2*delta7)4299Ahmb

Allele Symbol: Tg(SMN2*delta7)4299Ahmb

Allele Name	transgene insertion 4299, Arthur H M Burghes
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

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:

Neurobiology Research
- Spinal Muscular Atrophy (SMA)
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

References

Additional - Grm7^{Tg(SMN2)89Ahmb} related

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

Additional - Tg(SMN2*delta7)4299Ahmb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Tg(SMN2)
- Standard PCR:Grm7
- Standard PCR:Tg(SMN2*)
- Standard PCR:Tg(Myh6-cre)
- Separated PCR:Smn1
- Standard PCR:Smn1
- Separated MCA:Smn1
- Standard PCR:Tg(Myh6-cre)
- Standard PCR:Grm7 Alternate1
- QPCR:Tg(SMN2*)
- Probe:Grm7-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice heterozygous for Smn1^{tm3(SMN2/Smn1)Mrph}, homozygous for Tg(SMN2*delta7)4299Ahmb and homozygous for Tg(SMN2)89Ahmb may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the SMNΔ7;SMN2;Smn^Res , SMNΔ7;SMN2;Smn^COIN , 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.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or wildtype for Smn1<tm3(SMN2/Smn1)Mrph>, Homozygous for Tg(SMN2*delta7)4299Ahmb, Homozygous for Tg(SMN2)89Ahmb/J

Related Products and Services

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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The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:SMNΔ7;SMN2;SmnRes , SMNΔ7;SMN2;SmnCOIN , Moderate Type II SMA Rescue , Delta 7 mouse with hybrid rescue allele

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Grm7Tg(SMN2)89Ahmb

Allele Symbol: Grm7Tg(SMN2)89Ahmb

Tg(SMN2*delta7)4299Ahmb

Allele Symbol: Tg(SMN2*delta7)4299Ahmb

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

References

Additional - Grm7Tg(SMN2)89Ahmb related

Additional - Smn1tm3(SMN2/Smn1)Mrph related

Additional - Tg(SMN2*delta7)4299Ahmb related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:SMNΔ7;SMN2;Smn^Res , SMNΔ7;SMN2;Smn^COIN , Moderate Type II SMA Rescue , Delta 7 mouse with hybrid rescue allele

Grm7^{Tg(SMN2)89Ahmb}

Allele Symbol: Grm7^{Tg(SMN2)89Ahmb}

Smn1^{tm3(SMN2/Smn1)Mrph}

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

Additional - Grm7^{Tg(SMN2)89Ahmb} related

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