Overview

Also Known As:Burgheron

This virtual strain is no longer available. Search the JAX Mice database for other mouse models useful for studying Spinal Muscular Atrophy.

Genetic overview

Genetic Background	Generation

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)

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence, Humanized sequence)	Smn1	survival motor neuron 1

Research Applications

Neurobiology Research
Research Tools
Developmental Biology Research

View All Research Applications

Details

Important Note

The Jackson Laboratory will not distribute triple mutant mice. Instead, we will distribute the individual lines; that is, females homozygous for the Tg(SMN2)89 transgene and heterozygous for Smn1^tm1Msd (see Stock No. 007949) and males heterozygous for Smn1^{tm5(Smn1/SMN2)Mrph} (see Stock No. 008604).

Detailed Description

Stock No. 014561 breeding pairs allow a researcher to generate FVB.SMN2;Smn1^-/C mice; the FVB/NJ-congenic Burgheron SMA model strain with one copy of the Tg(SMN2)89 transgene and are compound heterozygous at the Smn1 locus for the Smn1 null allele and Smn1 allele C (Smn1^-/C).

Compound heterozygous (Smn1^-/C) animals harbor the Smn1 null targeted mutation (Smn1^tm1Msd; also called Smn1^-) on one homologous chromosome, and the Smn1 allele C (Smn1^{tm5(Smn1/SMN2)Mrph}; also called Smn1^C) on the other homologous chromosome. Smn1^-/C mice have an intermediate level of SMN expression that falls between that of Smn1^-/- and Smn1^C/C.

The phenotype of FVB.SMN2;Smn1^-/C mice is the intermediate type II/III Spinal Muscular Atrophy. Mean survival is ~98.5 days for females and ~102 days for males. Tail necrosis leads to tail loss by ~45 days of age. Other characteristic SMA phenotypes in the Burgheron model include cardiomyopathy, reduced numbers of functional motor units, and delayed neuromuscular junction maturation.

The phenotype of the parental mouse lines used to generate FVB.SMN2;Smn1^-/C mice (Stock No. 014561) are each briefly described below.

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 (Stock Nos. 005024 and 007949). FVB.SMN2+/+;Smn-/- mice exhibit perinatal and complete embryonic lethality that worsens with increased backcross generations onto FVB/NJ. Also note, Stock No. 005024 does not survive as hemizygous for the Tg(SMN2)89 transgene and homozygous for the Smn1 null allele.

The Smn1^C hybrid allele contains two tandem Smn1/SMN2 genes. Homozygous FVB/N-congenic Smn1^C/C mice (Stock No. 008604) exhibit a mild SMA phenotype due to the preferential splicing of the Δ7-SMN gene product over the full-length SMN product.

Development

FVB.SMN2;Smn1^-/C mice harbor the Tg(SMN2)89 transgene and are compound heterozygous for the the Smn1 null allele and Smn allele C. The Jackson Laboratory will not distribute animals with this genotype. Instead, we will distribute as the following breeding pair: females homozygous for the Tg(SMN2)89 transgene (SMN2+/+) and heterozygous for the Smn1^tm1Msd null allele (Smn+/-) and males heterozygous for the Smn1^{tm5(Smn1/SMN2)Mrph} allele (Smn1^C/+). Each component is described below.

The creation of the Tg(SMN2)89 transgene (SMN2) and Smn1 null targeted mutation (Smn1^tm1Msd; also called Smn1^-) are described for the severe type I SMA mouse model on an FVB/NJ fully congenic background; Stock No. 007949. Note the Tg(SMN2)89 transgene insertion site in on chromosome 6. Stock No. 007949 is bred to and maintained upon an FVB/NJ-congenic background.

The creation of the Smn1 allele C (Smn1^{tm5(Smn1/SMN2)Mrph}; also called Smn1^C) is described as Stock No. 008604. Briefly, the Smn1^C contains two tandem Smn1/SMN2 genes. Stock No. 008064 is maintained upon an FVB/NJ-congenic background.

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	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
Expressed Gene	Smn1, survival motor neuron 1, mouse, laboratory
Site of Expression	Smn1 is normally expressed in motor neurons, particularly in the spinal chord.

Control Suggestions

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

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	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

Smn1^{tm5(Smn1/SMN2)Mrph}

Allele Symbol: Smn1^{tm5(Smn1/SMN2)Mrph}

Allele Name	targeted mutation 5, Andrew Murphy
Allele Type	Targeted (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Smn allele C
Gene Symbol and Name	Smn1, survival motor neuron 1
Gene Synonym(s)
Expressed Gene	SMN2, survival of motor neuron 2, centromeric, human
Expressed Gene	Smn1, survival motor neuron 1, mouse, laboratory
Site of Expression	Smn1 is normally expressed in motor neurons, particularly in the spinal chord.
Strain of Origin	(129S6/SvEvTac x C57BL/6NTac)F1
Chromosome	13
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.
Mutations Made By	Andrew Murphy, Regeneron Pharmaceuticals, Inc.

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

Genotype: Smn1^tm1Msd related

Neurobiology Research
- Spinal Muscular Atrophy (SMA)

Mammalian Phenotype Terms by Genotype

References

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

Additional - Smn1^tm1Msd related

Additional - Smn1^{tm5(Smn1/SMN2)Mrph} related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(SMN2*)
- Standard PCR:Smn1 Alternate
- Genotyping resources and troubleshooting
Breeding Considerations

The Tg(SMN2)89 transgene on chromosome 6 and the Smn1 targeted mutations on chromosome 13 are not linked and will segregate independently.

FVB.SMN2;Smn1^-/C mice harbor the Tg(SMN2)89 transgene and are compound heterozygous for the the Smn1 null allele and Smn allele C. The Jackson Laboratory will not distribute animals with this genotype. Instead, breeding pairs offered by The Jackson Laboratory Repository are females homozygous for the Tg(SMN2)89 transgene (SMN2+/+) and heterozygous for the Smn1^tm1Msd null allele (Smn+/-) and males heterozygous for the Smn1^{tm5(Smn1/SMN2)Mrph} allele (Smn1^C/+).

These breeding pairs are phenotypically normal and do not exhibit symptoms of neuropathology.

Offspring resulting from the mating of these breeder pairs can possess the following genotypes:
1. SMN2;Smn1^-/C: Hemizygous for the transgene and compound heterozygous at the Smn1 locus for the Smn1 null allele and Smn1 allele C (25%)

2. SMN2;Smn1^+/-: Hemizygous for the transgene and heterozygous for the Smn1 null allele (25%)

3. SMN2;Smn1^C/+: Hemizygous for the transgene and heterozygous for the Smn1 allele C (25%)

4. SMN2;Smn1^+/+: Hemizygous for the transgene and wildtype for both Smn1 targeted mutations (25%)

Mice that are hemizygous for the transgene and compound heterozygous will display the SMA-like phenotype.
- Additional Breeding and Husbandry Support

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:Burgheron

Genetic overview

Research Applications

Important Note

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Smn1tm1Msd

Allele Symbol: Smn1tm1Msd

Grm7Tg(SMN2)89Ahmb

Allele Symbol: Grm7Tg(SMN2)89Ahmb

Smn1tm5(Smn1/SMN2)Mrph

Allele Symbol: Smn1tm5(Smn1/SMN2)Mrph

Disease Terms

Research Areas By Phenotype

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

Genotype: Smn1tm1Msd related

Mammalian Phenotype Terms by Genotype

References

Additional - Grm7Tg(SMN2)89Ahmb related

Additional - Smn1tm1Msd related

Additional - Smn1tm5(Smn1/SMN2)Mrph related

Genotyping Protocols

Breeding Considerations

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}

Smn1^{tm5(Smn1/SMN2)Mrph}

Allele Symbol: Smn1^{tm5(Smn1/SMN2)Mrph}

Genotype: Smn1^tm1Msd related

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

Additional - Smn1^tm1Msd related

Additional - Smn1^{tm5(Smn1/SMN2)Mrph} related