Overview

Also Known As:SMN2 SMN- HB9-eGFP

Mice of this strain carry a survival motor neuron 1 knock-out , a transgene consisting of the human survival motor neuron 2 (SMN2) gene and promoter, and a transgene expressing GFP in axons, dendrites and processes of spinal motor neurons of embryonic mice. Symptoms and neuropathology are similar to those of patients afflicted with type I proximal spinal muscular atrophy (SMA).

Genetic overview

Genetic Background	Generation

Tg(Hlxb9-GFP)1Tmj

Allele Type
Transgenic (Reporter)

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

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Research Applications

Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Similar to Stock No. 005024, mice that are homozygous for the targeted mutant Smn1 allele and carry the SMN2 transgene exhibit symptoms and neuropathology similar to patients afflicted with type I proximal spinal muscular atrophy (SMA). As an addition to Stock No. 005024, this line carries a transgene containing a Green Fluorescent Protein (GFP) under the direction of the mouse Hlxb9 promoter. Transgenic mice display distinct expression of GFP in dendrites, axons and soma of spinal motor neurons, allowing identification, isolation and purification of spinal motor neurons by FACS. GFP expression mimics endogenous HLXB9 expression pattern. Fluorescence is detected in axons, dendrites and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice. This mutant mouse strain represents a model that may be useful for purification and in vivo tracking of spinal motor neurons. Mice homozygous for the Hlxb9-GFP transgenic insert are reportedly viable, fertile, do not display any gross behavioral abnormalities, but are smaller in size than wild-type littermates. Homozygous pups born to homozygous females have a high mortality rate. In the initial characterization by the donating investigator, mice that are homozygous for the targeted mutant Smn1 allele and carry the SMN2 transgene exhibit symptoms and mice were either stillborn or survived 4-6 days. Mice that died at or shortly after birth were slightly smaller (1.33 g. vs. 1.51 g.) than normal littermates. Mice that survive for several days are indistinguishable from normal littermates in the first 48 hours, after which they exhibit decreased suckling and movement, labored breathing and tremoring limbs. Mice succumbing at this later time point are noticeably smaller than normal littermates (1.47 g vs. 4.59). A bell-shaped trunk is also noticeable in affected mice, presumably from intercostal muscle weakness, a characteristic of type I SMA. Histological analysis indicates that affected mice that survive to day 5 exhibit a loss of motor neurons from spinal cord (35%) and facial nucleus (40%). A large number of cells with pyknotic nuclei are observed in these tissues. Immunohistochemical analysis indicates low-level expression of the SMN2 protein in the tissues examined (brain, liver, spinal cord) and an absence or near absence of intranuclear aggregates of the SMN protein (gems?). Homozygous mice bearing the Smn1 targeted mutation without a copy of the SMN2 transgene display an embryonic lethal phenotype with developmental arrest occurring prior to implantation.

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-/-).

Distribution of this model is supported by the Spinal Muscular Atrophy Foundation.

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 Smn1 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 SMN2 transgene was created in the laboratory of Dr. Arthur Burghes at The 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. Transgenic SMN2 mice from founder line 89 were established and then bred to the Smn1 mutant mice. The double mutant mice were then backcrossed to FVB/N for at least 5 generations. Next, these mice were crossed Stock No. 005029 which consisted of a transgenic construct containing a 9kb sequence of the 5' portion of the mouse Hlxb9 gene, a GFP open reading frame, and bovine growth hormome polyadenylation site sequence.

Expression Data

Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Dendrites, axons, and soma of spinal motor neurons display distinct expression of GFP. GFP expression mimics endogenous HLXB9 expression pattern. Fluorescence is detected in axons, dendrites, and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice.
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

None Available

Additional Information

Considerations for Choosing Controls

Genetics

Tg(Hlxb9-GFP)1Tmj

Allele Symbol: Tg(Hlxb9-GFP)1Tmj

Allele Name	transgene insertion 1, Thomas M Jessell
Allele Type	Transgenic (Reporter)
Allele Synonym(s)	Gfp-HB9; Hb9::EGFP; Hb9:GFP-1B; Hb9-eGFP; Hb9-Gfp; Hlxb9:GFP
Gene Symbol and Name	Tg(Hlxb9-GFP)1Tmj, transgene insertion 1, Thomas M Jessell
Gene Synonym(s)
Promoter	Mnx1, motor neuron and pancreas homeobox 1, mouse, laboratory
Expressed Gene	GFP, Green Fluorescent Protein,
Site of Expression	Dendrites, axons, and soma of spinal motor neurons display distinct expression of GFP. GFP expression mimics endogenous HLXB9 expression pattern. Fluorescence is detected in axons, dendrites, and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice.
Strain of Origin	(C57BL/6 x CBA)F1
Chromosome	15
General Note	Homozygous transgenic mice on a genetic background that involves C57BL/6 and CBA are viable and fertile. They do not display any gross behavioral abnormalities, but are smaller in size than wildtype littermates. Homozygous pups born to homozygous females have a high mortality rate. Transgenic mice display distinct expression of GFP in dendrites, axons, and soma of spinal motor neurons, allowing identification, isolation and purification of spinal motor neurons by FACS. GFP expression mimics endogenous HLXB9 expression pattern. Fluorescence is detected in axons, dendrites and processes of spinal motor neurons at embryonic day 9.5 to postnatal day 10 aged mice.
Molecular Note	The transgenic construct contains a 9kb sequence of the 5' portion of the mouse Hlxb9 (Mnx1) gene, a 5' splice substrate, an enhanced Green Fluorescent Protein (EGFP) open reading frame, and a bovine growth hormome polyadenylation site sequence. Line 1 contains 10 to 11 tandem copies of the transgene. The expression pattern of this transgene is the same as that for the endogenous gene from which the promoter is derived.
Mutations Made By	Ivo Lieberam, Columbia University/HHMI

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

Research Areas By Phenotype

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

Neurobiology Research
- Fluorescent protein expression in neural tissue
- Spinal Muscular Atrophy (SMA)
- Neurodegeneration
Research Tools
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: neurons
- Fluorescent Proteins
- Neurobiology Research
  - cell marker

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 - Tg(Hlxb9-GFP)1Tmj related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Tg(SMN2)
- Probe:Fluorescent Proteins (Generic GFP)
- Standard PCR:Grm7
- Standard PCR:Smn1
- Separated PCR:Smn1
- Standard PCR:Grm7 Alternate1
- Standard PCR:Fluorescent Proteins (Generic GFP)
- Probe:Grm7-Probe
- Genotyping resources and troubleshooting
Breeding Considerations

The Smn1 (survival motor neuron 1) gene on Chr 13 and the randomly inserted transgene are not linked and will segregate independently. Breeding pairs offered by The Jackson Laboratory are homozygous for the transgene and heterozygous for the targeted Smn1 mutation with one parental genotype containing the Hlxb9-GFP transgene. These breeding pairs are phenotypically normal and do not exhibit symptoms of neuropathology. Mice that are homozygous for the SMN2 transgene and homozygous for the targeted mutation will display the SMA-like phenotype. Mice homozygous for the SMN2 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.
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 SMN2 SMN- HB9-eGFP mouse strain in a publication, please cite the originating article(s) and include JAX stock #006570 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
	Homozygous for Tg(SMN2)89Ahmb, Heterozygous or wildtype for Smn1<tm1Msd>, Hemizygous or Non carrier for Tg(Hlxb9-GFP)1Tmj

Related Products and Services

Frozen Mouse Embryo	STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Hlxb9-GFP)1Tmj/J	$2595.00
Frozen Mouse Embryo	STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Hlxb9-GFP)1Tmj/J	$2595.00
Frozen Mouse Embryo	STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Hlxb9-GFP)1Tmj/J	$3373.50
Frozen Mouse Embryo	STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Hlxb9-GFP)1Tmj/J	$3373.50

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Also Known As:SMN2 SMN- HB9-eGFP

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Tg(Hlxb9-GFP)1Tmj

Allele Symbol: Tg(Hlxb9-GFP)1Tmj

Grm7Tg(SMN2)89Ahmb

Allele Symbol: Grm7Tg(SMN2)89Ahmb

Smn1tm1Msd

Allele Symbol: Smn1tm1Msd

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 - Tg(Hlxb9-GFP)1Tmj 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

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

Additional - Smn1^tm1Msd related