Overview

Also Known As:FVB.SMN2;Smn- , Severe Type I SMA , Burghes' Severe Model FVB/NJ congenic

Mice that are homozygous for the Tg(SMN2)89 transgene and the Smn1 null mutation exhibit symptoms and neuropathology similar to patients with severe type I proximal spinal muscular atrophy (SMA). Homozygous mice fully congenic on the FVB/NJ genetic background (N10; Stock No. 007949) may exhibit phenotype differences compared to the incipient congenic FVB/N homozygous colony (N5; Stock No. 005024).

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)

Smn1^tm1Msd

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

View Genetics

Research Applications

Neurobiology Research
Research Tools
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

FVB.SMN2;Smn- mice are available with different amounts of backcrossing onto the FVB/N genetic background: FVB/NJ fully congenic FVB.SMN2;Smn- mice are backcrossed ten generations (N10; Stock No. 007949) while incipient congenic FVB.SMN2;Smn- mice are backcrossed five generations (N5; Stock No. 005024).

Detailed Description

FVB/N-congenic mice homozygous for the Tg(SMN2)89 transgene (SMN2+/+) and homozygous for the Smn1^tm1Msd mutation (Smn-/-) are a severe type I SMA mouse model. Homozygous mice fully congenic on the FVB/N genetic background (N10; Stock No. 007949) may exhibit phenotype differences compared to the incipient congenic FVB/N homozygous colony (N5; Stock No. 005024). The phenotype differences between these two strains, if any, have not yet been completely characterized (June 2013). Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene (SMN2+/-) and homozygous for the Smn1^tm1Msd mutation (Smn-/-).

Development

These B6.SMN2;Smn- mice harbor the Tg(SMN2)89 transgene and the Smn1 null allele (Smn1^tm1Msd). The creation of the transgene and targeted mutation are described for the severe type I SMA mouse model on an incipient FVB/N congenic background; Stock No. 005024. Note the Tg(SMN2)89 transgene insertion site in on chromosome 6. FVB.SMN2;Smn- mice that had been backcrossed onto FVB/N for five generations (N5; Stock No. 005024) were obtained and then backcrossed onto FVB/NJ for additional generations. The strain after ten generations of backcrossing is FVB/NJ fully congenic FVB.SMN2;Smn- (N10; Stock No. 007949).

Expression Data

Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Site of Expression	Grm7^{Tg(SMN2)89Ahmb}
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.

Control Suggestions

001800 FVB/NJ

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
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

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

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Werdnig-Hoffmann disease

Research Areas By Phenotype

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

Genotype: Smn1^tm1Msd related

Neurobiology Research
- Spinal Muscular Atrophy (SMA)

Neurobiology Research
- Neuromuscular defects
- Spinal Muscular Atrophy (SMA)
- lacZ expression in neural tissue
- Ataxia (Movement) Defects
- Neurodegeneration
- Neurodevelopmental Defects
Research Tools
- Neurobiology Research
- lacZ Expression
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/?
involves: 129P2/OlaHsd * C57BL/6J * FVB

behavior/neurological phenotype

abnormal suckling behavior
- mice that survived 4-6 days displayed a decrease or lack of suckling by 48 hours postnatal

bradykinesia
- mice that survived 4-6 days showed a decrease in movement within 48-72 hours postnatal

tremors
- mice that survived 4-6 days showed a marked tremor within 72-96 hours postnatal

respiratory system phenotype

respiratory distress
- mice that survived 4-6 days displayed labored breathing by 48 hours postnatal

mammalian phenotype

muscle phenotype
- Normal - no musculature atrophy was detected in the quadriceps or gastrocnemius of mice that survived 4-6 days

mortality/aging

perinatal lethality, incomplete penetrance
- a slightly less than expected frequency of mice with this genotype suggests that some mice may be dying in utero
- in few cases, mice of this genotype survived up to 6 days of age
- the majority of mice were stillborn or died within 6 hours of birth

postnatal lethality, complete penetrance
- in few cases, mice of this genotype survived up to 6 days of age

nervous system phenotype

motor neuron degeneration
- dramatic loss of motor neurons were observed in spinal cord (~35% loss) and facial nucleus(~40% loss) at postnatal day 5
- normal numbers of motor neurons were observed in spinal cord and facial nucleus in animals at postnatal day 1

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
B6.Cg-Grm7 Smn1

growth/size/body region phenotype

decreased body weight
- at P5

mortality/aging

lethality, complete penetrance
- Background Sensitivity - double homozygotes are not found postnatally unlike when mice are on an inbred FVB/NJ background

postnatal lethality, complete penetrance
- mice do not survive past 8 days with a mean survival of 5 days

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
B6.Cg-Grm7 Smn1

mortality/aging

postnatal lethality, complete penetrance
- mice do not survive past 2 days with a mean survival of 1 day

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
involves: 129P2/OlaHsd * FVB/N

cardiovascular system phenotype

thin interventricular septum
- reduction in width of the interventricular septum at E17.5

thin ventricular wall
- hearts have a thin and branched left ventricular wall at E17.5

mortality/aging

prenatal lethality, incomplete penetrance
- fewer than the expected numbers of mutants are seen at birth

Genotype: Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd/Smn1^tm1Msd
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

lethality, complete penetrance
- Background Sensitivity - double homozygotes are not found postnatally unlike when mice are on an inbred FVB/NJ background

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}
FVB.Cg-Grm7 Smn1/J

growth/size/body region phenotype

decreased body weight

mammalian phenotype

mortality/aging
- Background Sensitivity - double homozygotes are detected postnatally unlike when mice are on an inbred C57BL/6J background or on a mixed background involving predominantly 129 and C57BL/6J

mortality/aging

postnatal lethality
- mean lifespan is 7 days

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

nervous system phenotype

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

abnormal neuromuscular synapse morphology
- many endplates are partially occupied or vacant unlike in wild-type mice

References

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

Additional - Smn1^tm1Msd related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Smn1
- Standard PCR:Grm7 Alternate1
- QPCR:SMN Genomic
- Probe:Grm7-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

The Tg(SMN2)89 transgene on chromosome 6 and the Smn1 null targeted mutation (Smn1^tm1Msd) on chromosome 13 are not linked and will segregate independently. Breeding pairs offered by The Jackson Laboratory Repository are homozygous for the transgene and heterozygous for Smn1^tm1Msd. 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 the transgene and homozygous for the targeted mutation (25%)

2. Homozygous for the transgene and heterozygous for the targeted mutation (50%)

3. Homozygous for the transgene and wildtype at the Smn1 locus (25%)

Mice that are homozygous for the transgene and homozygous for the targeted mutation will display the SMA-like phenotype. Mice homozygous for the transgene and heterozygous for the targeted mutation will not display the SMA-like phenotype but can be mated with each other to generate additional affected mice. Mice homozygous for the transgene and wildtype at the Smn1 locus will also not exhibit an SMA-like phenotype but can be employed as control mice depending on the nature of the experiment. The Jackson Laboratory Repository also distributes mice that are homozygous for the transgene and wildtype at the Smn1 locus.

Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene (SMN2+/-) and homozygous for the Smn1^tm1Msd mutation (Smn-/-).
- Additional Breeding and Husbandry Support
Citation
When using the FVB.SMN2;Smn- , Severe Type I SMA , Burghes' Severe Model FVB/NJ congenic mouse strain in a publication, please cite the originating article(s) and include JAX stock #007949 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
	Hemizygous for Tg(SMN2)89Ahmb, Heterozygous or Wildtype for Ahmb Smn1<tm1Msd>

Related Products and Services

Frozen Mouse Embryo	FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd>/2J Frozen Embryos	$2595.00
Frozen Mouse Embryo	FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd>/2J Frozen Embryos	$2595.00
Frozen Mouse Embryo	FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd>/2J Frozen Embryos	$3373.50
Frozen Mouse Embryo	FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd>/2J Frozen Embryos	$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.

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Questions about Terms of Use

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Licensing Information

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Also Known As:FVB.SMN2;Smn- , Severe Type I SMA , Burghes' Severe Model FVB/NJ congenic

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Grm7Tg(SMN2)89Ahmb

Allele Symbol: Grm7Tg(SMN2)89Ahmb

Smn1tm1Msd

Allele Symbol: Smn1tm1Msd

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

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/?involves: 129P2/OlaHsd * C57BL/6J * FVB

behavior/neurological phenotype

respiratory system phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89AhmbB6.Cg-Grm7 Smn1

growth/size/body region phenotype

mortality/aging

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7+B6.Cg-Grm7 Smn1

mortality/aging

Genotype: Smn1tm1Msd/Smn1tm1Msd Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmbinvolves: 129P2/OlaHsd * FVB/N

cardiovascular system phenotype

mortality/aging

Genotype: Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmb Smn1tm1Msd/Smn1tm1Msdinvolves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

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

growth/size/body region phenotype

mammalian phenotype

mortality/aging

muscle phenotype

nervous system phenotype

References

Additional - Grm7Tg(SMN2)89Ahmb related

Additional - Smn1tm1Msd 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Grm7^{Tg(SMN2)89Ahmb}

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

Smn1^tm1Msd

Allele Symbol: Smn1^tm1Msd

Genotype: Smn1^tm1Msd related

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/?
involves: 129P2/OlaHsd * C57BL/6J * FVB

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
B6.Cg-Grm7 Smn1

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
B6.Cg-Grm7 Smn1

Genotype: Smn1^tm1Msd/Smn1^tm1Msd Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
involves: 129P2/OlaHsd * FVB/N

Genotype: Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd/Smn1^tm1Msd
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6J * FVB/N

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

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

Additional - Smn1^tm1Msd related