Overview

Also Known As:Moderate Type II SMA mice, SMNdelta7;SMN2;Smn-/-, FVB.SMNΔ7;SMN2;Smn- , Moderate Type II SMA , Delta 7 mouse incipient congenic

Mice that are homozygous for the Smn targeted mutant lacZ reporter allele and homozygous for the two transgenic alleles exhibit symptoms and neuropathology similar to patients afflicted with proximal spinal muscular atrophy (SMA). Triple homozygous mice on the FVB/N genetic background are noticeably smaller than normal littermates at birth and show progressive muscle weakness.

Our preclinical efficacy testing services offer scientific expertise and an array of target-based and phenotype-based outcome measures, both in vivo and at endpoint, for flexible study designs and assay development in mouse models of Spinal Muscular Atrophy. See our full service platform.

Donating Investigator

Arthur H.M. Burghes, The Ohio State University

Genetic overview

Genetic Background	Generation
	N6+F41 (2021-01-14 00:00:00)

Smn1^tm1Msd

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Smn1	survival motor neuron 1

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)

View Genetics

Research Applications

Neurobiology Research
Research Tools
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$270.00 Domestic price for female 4-week

540.00 Domestic price for breeder pair

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Details

Detailed Description

This triple mutant mouse harbors two transgenic alleles and a single targeted mutant. The Tg(SMN2*delta7)4299Ahmb allele consists of a SMA 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 Smn allele and homozygous for the two transgenic alleles exhibit symptoms and neuropathology similar to patients afflicted with proximal spinal muscular atrophy (SMA). At birth, triple mutants are noticeably smaller than normal littermates. By day 5, signs of muscle weakness are apparent and become progressively more pronounced over the following week as the mice display an abnormal gait, shakiness in the hind limbs and a tendency to fall over. In 2006, mean survival was originally reported to be ~13 days. Cohorts tested at The Jackson Laboratory in 2013 show death by ~15-22 days (mean survival of 17.7 days).

Immunocytochemical analysis indicates that dystrophin expression is normal, however fibers isolated from the gastrocnemius muscle of a 14 day old triple mutant clearly show evidence of atrophy.

Importation of this model was supported by the Spinal Muscular Atrophy Foundation. Creation and development was supported by the National Institutes of Health, the Deutsche Forschungsgemeinschaft to M.S., Families of SMA, the Preston fund, the Madison fund, the Mathew fund and the Muscular Dystrophy Association of America.

Development

The targeted mutant allele was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the endogenous mouse Smn gene was disrupted by employing a targeting vector encoding a neomycin cassette and a lacZ gene fused to the first 40 nucleotides of the disrupted exon to permit expression of the lacZ gene in tissues where Smn is normally expressed. The construct was electroporated into 129P2/OlaHsd-derived E14Tg2a-IV embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations.
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 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. Founder animal 89 was mated to mice heterozygous for the targeted mutation of the endogenous mouse Smn gene. These double mutants were in turn mated with mice bearing the SMNdelta7 transgenic allele. The triple mutant was then backcrossed to FVB/N for at least 6 generations.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	The expression of the lacZ gene in tissues where Smn is normally expressed was noted.
Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Site of Expression	Grm7^{Tg(SMN2)89Ahmb}
Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Site of Expression	Tg(SMN2*delta7)4299Ahmb

Control Suggestions

Appropriate controls depend on the nature of the experiment. FVB/NJ mice (Stock No. 001800) may be used as controls.

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Le TT; Pham LT; Butchbach ME; Zhang HL; Monani UR; Coovert DD; Gavrilina TO; Xing L; Bassell GJ; Burghes AH. 2005. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14(6):845-57PubMed: 15703193 MGI: J:97103

View All References

Genetics

Smn1^tm1Msd

Allele Symbol: Smn1^tm1Msd

Allele Name	targeted mutation 1, Michael Sendtner
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	SMN^-
Gene Symbol and Name	Smn1, survival motor neuron 1
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	The expression of the lacZ gene in tissues where Smn is normally expressed was noted.
Strain of Origin	129P2/OlaHsd
Chromosome	13
Molecular Note	A lacZ-neo cassette was inserted into exon 2 by homologous recombination resulting in an in-frame fusion of lacZ to exon 2. Homozygous mutant embryos were identified up to 80 hours post coitum. The expression of the lacZ gene in tissues where Smn is normally expressed was noted.
Mutations Made By	Michael Sendtner

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	Grm7^{Tg(SMN2)89Ahmb}
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

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Werdnig-Hoffmann disease

Research Areas By Phenotype

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

Neurobiology Research
- Neuromuscular defects
- lacZ expression in neural tissue
- Ataxia (Movement) Defects
- Neurodevelopmental Defects
- Neurodegeneration
Research Tools
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: multiple
  - Tissue/Cell Markers: neurons
- Neurobiology Research
  - cell marker
- lacZ Expression
Developmental Biology Research
- Neurodevelopmental Defects

Genotype: Smn1^tm1Msd related

Neurobiology Research
- Spinal Muscular Atrophy (SMA)

Mammalian Phenotype Terms by Genotype

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

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/0
FVB.Cg-Grm7 Smn1 Tg(SMN2delta7)4299Ahmb/J

cardiovascular system phenotype

cardiac interstitial fibrosis
- mutants exhibit an increase in cardiac fibrosis compared to unaffected wild-type controls

thin interventricular septum

growth/size/body region phenotype

decreased body weight

mortality/aging

postnatal lethality
- mean lifespan is 13 days

muscle phenotype

decreased skeletal muscle fiber size

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺ Tg(SMN2delta7)4299Ahmb/0
FVB.Cg-Grm7 Smn1 Tg(SMN2delta7)4299Ahmb

mortality/aging

postnatal lethality, complete penetrance
- mice do not survive past 16 days with a mean survival of 10 days

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/Tg(SMN2delta7)4299Ahmb
FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb

behavior/neurological phenotype

impaired balance
- by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice

impaired limb coordination
- by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice

impaired righting response
- at P5

abnormal gait
- at P10, mice exhibit abnormal gait with fibrillation of the hindlimbs

growth/size/body region phenotype

decreased body weight
- at P5

mortality/aging

postnatal lethality, complete penetrance
- mice do not survive past 17 days with a mean survival of 13 days

muscle phenotype

skeletal muscle fiber atrophy
- at P14, muscle fibers of the gastrocnemius are small due to atrophy

nervous system phenotype

abnormal neuromuscular synapse morphology
- at P14, many neuromuscular junctions are partially innervated or not innervated
- the diameter of neuromuscular junctions is smaller than in wild-type mice

decreased motor neuron number
- in the lumbar region of the spinal cord at P9
- Normal - however, spinal motor neuron numbers at P4 are normal

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/Tg(SMN2delta7)4299Ahmb
FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb/J

cardiovascular system phenotype

abnormal blood flow velocity
- cle to the lungs
- echocardiography indicates that P6 mice exhibit deficiencies in blood flow out of the right ventricle at the pulmonary valve, with decreased peak velocity and peak gradient, indicating a reduction in pumping efficiency and blood flow from the right ventricle to the lungs

prolonged PR interval
- at P4, mice have a first-degree heart block characterized by elongated PR interval durations
- at P10, sharp increase in the PR interval and breakdown of cardiac rhythm as mutants exhibit progressive heart block

dilated cardiomyopathy

abnormal heart morphology
- hearts appear flaccid and lack defined shape and gross attenuation of walls at P10 and P13

increased heart rate variability
- as mice near end of life, they display a large increase in heart rate variability, ultimately displaying adjacent RR intervals that are highly inconsistent

decreased heart rate
- bradyarrhythmia is characterized by progressive heart block and reduced ventricular depolarization efficiency
- mice present bradycardia as early as 2 days of age, before neuromuscular symptoms

prolonged QRS complex duration
- elongation of the time of ventricular depolarization through an increase in QRS interval duration beginning at P4

growth/size/body region phenotype

decreased body size

weight loss
- begin to lose weight at around P10

mortality/aging

postnatal lethality, complete penetrance
- average survival of about 2 weeks

muscle phenotype

decreased skeletal muscle fiber diameter
- muscle fiber diameter is decreased in both slow- and fast-twitch muscles compared to in wild-type mice

dilated cardiomyopathy

nervous system phenotype

abnormal neuromuscular synapse morphology
- mice exhibit both post- and pre-synaptic pathology at motor neuron endplates
- many endplates are partially occupied or vacant unlike in wild-type mice

abnormal sympathetic system morphology
- TH staining of the heart to visualize sympathetic innervation indicates that mutants exhibit fewer major neuronal branches and they appear thinner and less distinct

abnormal innervation pattern to muscle
- mice preferentially lack innervation of the caudal band of the levator auris longus

References

Le TT; Pham LT; Butchbach ME; Zhang HL; Monani UR; Coovert DD; Gavrilina TO; Xing L; Bassell GJ; Burghes AH. 2005. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum Mol Genet 14(6):845-57PubMed: 15703193 MGI: J:97103

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

Additional - Smn1^tm1Msd related

Additional - Tg(SMN2*delta7)4299Ahmb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Tg(SMN2)
- Standard PCR:Smn1
- Standard PCR:Grm7
- Standard PCR:Tg(SMN2*)
- Standard PCR:Smn1
- QPCR:Tg(SMN2*)
- Probe:Grm7-Probe
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The Tg(SMN2)89 transgene insertion into the glutamate receptor metabotropic 7 locus (Grm7^{Tg(SMN2)89Ahmb}) on chromosome 6, the Smn1 null targeted mutation (Smn1^tm1Msd) on chromosome 13 and the randomly inserted Tg(SMN2*delta7)4299Ahmb transgene are not linked and will segregate independently.
Breeding pairs offered by The Jackson Laboratory Repository are homozygous for both transgenes (Δ7SMN^+/+;SMN2^+/+) and either heterozygous for the null allele (Smn^+/-) or wildtype at the Smn1 locus (Smn^+/+). These breeding pairs are phenotypically normal and do not exhibit symptoms of neuropathology.
Offspring resulting from the mating of breeder pairs can possess the following genotypes:

1. Homozygous for both transgenes and heterozygous for the null allele (Δ7SMN^+/+;SMN2^+/+;Smn^+/- - 50%)
2. Homozygous for both transgenes and wildtype at the Smn1 locus (Δ7SMN^+/+;SMN2^+/+;Smn^+/+ - 50%)
Mice that are homozygous for the Smn1 null allele, Tg(SMN2)89 and Tg(SMN2*delta7)4299Ahmb will display the SMA-like phenotype. Mice heterozygous for the Smn1 null allele and homozygous for Tg(SMN2)89 and Tg(SMN2*delta7)4299Ahmb will not display the SMA-like phenotype - but can be mated with each other to generate additional affected mice. Mice wildtype at the Smn1 locus and homozygous for Tg(SMN2)89 and Tg(SMN2*delta7)4299Ahmb will also not exhibit an SMA-like phenotype - but can be employed as control mice depending on the nature of the experiment.
- Additional Breeding and Husbandry Support
Mating System
- See "Breeding Considerations"
Citation
When using the FVB.SMNΔ7;SMN2;Smn- , Moderate Type II SMA , Delta 7 mouse incipient congenic mouse strain in a publication, please cite the originating article(s) and include JAX stock #005025 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available Now

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Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Tg(SMN2*delta7)4299Ahmb, Homozygous for Tg(SMN2)89Ahmb, Heterozygous for Smn1<tm1Msd>

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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.

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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:Moderate Type II SMA mice, SMNdelta7;SMN2;Smn-/-, FVB.SMNΔ7;SMN2;Smn- , Moderate Type II SMA , Delta 7 mouse incipient congenic

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Smn1tm1Msd

Allele Symbol: Smn1tm1Msd

Grm7Tg(SMN2)89Ahmb

Allele Symbol: Grm7Tg(SMN2)89Ahmb

Tg(SMN2*delta7)4299Ahmb

Allele Symbol: Tg(SMN2*delta7)4299Ahmb

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

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

Genotype: Smn1tm1Msd related

Mammalian Phenotype Terms by Genotype

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/0FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb/J

cardiovascular system phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7+ Tg(SMN2*delta7)4299Ahmb/0FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb

mortality/aging

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299AhmbFVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299AhmbFVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb/J

cardiovascular system phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

References

Additional - Grm7Tg(SMN2)89Ahmb related

Additional - Smn1tm1Msd related

Additional - Tg(SMN2*delta7)4299Ahmb related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Smn1^tm1Msd

Allele Symbol: Smn1^tm1Msd

Grm7^{Tg(SMN2)89Ahmb}

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

Genotype: Smn1^tm1Msd related

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/0
FVB.Cg-Grm7 Smn1 Tg(SMN2delta7)4299Ahmb/J

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺ Tg(SMN2delta7)4299Ahmb/0
FVB.Cg-Grm7 Smn1 Tg(SMN2delta7)4299Ahmb

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/Tg(SMN2delta7)4299Ahmb
FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Tg(SMN2delta7)4299Ahmb/Tg(SMN2delta7)4299Ahmb
FVB.Cg-Grm7 Smn1 Tg(SMN2*delta7)4299Ahmb/J

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

Additional - Smn1^tm1Msd related