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).
Read More +Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Smn1 | survival motor neuron 1 |
Allele Type |
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Transgenic (Hypomorph, Inserted expressed sequence, Humanized sequence) |
Allele Type |
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Transgenic (Reporter) |
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 Smn1tm1Msd mutation (Smn-/-).
Distribution of this model is supported by the Spinal Muscular Atrophy Foundation.
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.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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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 | Grm7Tg(SMN2)89Ahmb |
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. |
Allele Name | targeted mutation 1, Michael Sendtner |
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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 |
Allele Name | transgene insertion 89, Arthur H M Burghes |
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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 | Grm7Tg(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 |
Allele Name | transgene insertion 1, Thomas M Jessell |
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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 |
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 Smn1tm1Msd mutation (Smn-/-).
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Tg(SMN2)89Ahmb, Heterozygous or wildtype for Smn1<tm1Msd>, Hemizygous or Non carrier for Tg(Hlxb9-GFP)1Tmj |
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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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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