These SMN2; Smn; HSA69-SMN mice may be useful for neuromuscular studies including spinal muscular atrophy (SMA).
Arthur H.M. Burghes, The Ohio State University
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 (Inserted expressed sequence, Humanized sequence) |
As described for SMA mice (see Stock No. 005024), mice homozygous for Smn1tm1Msd targeted mutation (Smn null allele) and human SMN2 low copy line 89 transgene exhibit symptoms, neuropathology, and early lethality similar to human type I proximal spinal muscular atrophy (SMA) patients. As an addition to that SMA model, this strain also carries the HSA-SMN transgene; with the human alpha-skeletal actin (HSA or ACTA1) promoter directing full-length human SMN expression at high levels in skeletal muscle. When the HSA-SMN transgene is derived from HSA69-SMN founder mice, skeletal muscle-specific SMN expression is preserved, and homozygous SMN2; Smn; HSA69-SMN mutant animals (Stock No. 008209) have the same phenotype as homozygous SMA mice. In contrast, expression of the HSA-SMN transgene derived from HSA63-SMN founder mice is leaky; with high SMN expression in heart and low SMN expression in spinal cord, brain, and liver. This additional SMN expression in neural cells rescues homozygous SMN2; Smn; HSA63-SMN mice (Stock No. 008203) from the severe SMA phenotype and significantly increases lifespan (average 160 days). Homozygous SMN2; Smn; HSA63-SMN mice also exhibit necrotic tail development with loss of the tail giving them a "hamster" appearance. These SMN2; Smn; HSA69-SMN mice may be useful for neuromuscular studies including spinal muscular atrophy (SMA).
These SMN2; Smn; HSA69-SMN mutant mice harbor a targeted mutation and two trangenes, all independently created.
The Smn1tm1Msd targeted mutation was created in the laboratory of Dr. Michael Sendtner at the University of Wurzburg, Germany. Exon 2 of the targeted gene was disrupted with 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. Chimeric animals were crossed to C57BL/6 for an unspecified number of generations.
The HSA-SMN transgene was designed with the human alpha-skeletal actin (HSA or ACTA1) promoter region, splice acceptor site from the SV40 VP1 intron, full-length humsn SMN cDNA (containing exons 1-8), and two SV40 polyA signals. This transgene was microinjected into fertilized FVB/N oocytes. Mice from founder line 69 (HSA69-SMN) were found to have 11 copies of the transgene.
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 and founder animals obtained. Transgenic SMN2 mice from founder line 89 were established and found to contain one copy of the transgene (also called SMN2 low copy line 89).
To generate the SMN2; Smn; HSA69-SMN mutant strain, FVB/N SMA carrier mice (heterozygous for the Smn1tm1Msd targeted mutation and homozygous for the SMN2 low copy line 89 transgene and backcrossed to FVB/N for at least 5 generations) were bred with FVB/N HSA69-SMN mice. Mice heterozygous for the targeted mutation, heterozygous for the HSA69-SMN transgene, and homozygous for the SMN2 low copy line 89 transgene were maintained for many generations prior to arrival at The Jackson Laboratory.
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 | SMN1, survival of motor neuron 1, telomeric, human |
Site of Expression | The expression of the lacZ gene in tissues where Smn is normally expressed was noted. |
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 69, Arthur H M Burghes |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | HSA69-SMN |
Gene Symbol and Name | Tg(ACTA1-SMN)69Ahmb, transgene insertion 69, Arthur H M Burghes |
Gene Synonym(s) | |
Promoter | ACTA1, actin, alpha 1, skeletal muscle, human |
Expressed Gene | SMN1, survival of motor neuron 1, telomeric, human |
Site of Expression | The expression of the lacZ gene in tissues where Smn is normally expressed was noted. |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | The HSA-SMN transgene was designed with the human alpha-skeletal actin (HSA or ACTA1) promoter region, splice acceptor site from the SV40 VP1 intron, full-length humsn SMN cDNA (containing exons 1-8), and two SV40 polyA signals. Mice from founder line 69 (HSA69-SMN) were found to have 11 copies of the transgene. |
When maintaining a live colony, mice heterozygous for the Smn1tm1Msd targeted mutation, homozygous for the SMN2 (line 89) transgene, and homozygous for the HSA69-SMN transgene may be bred together. The SMN2 (line 89) transgene is reported to have a single copy (thus homozygotes have 2 copies). The HSA69-SMN transgene copy number should be monitored as the phenotype of SMA models may be greatly affected by copy number variations.
When using the FVB.Cg-Grm7Tg(SMN2)89Ahmb Smn1tm1Msd Tg(ACTA1-SMN)69Ahmb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008209 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or wildtype for Smn1<tm1Msd>, Hemizygous or non carrier for Tg(ACTA1-SMN)69Ahmb, Hemizygous for Tg(SMN2)89Ahmb/J |
Frozen Mouse Embryo | FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(ACTA1-SMN)69Ahmb | $2595.00 |
Frozen Mouse Embryo | FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(ACTA1-SMN)69Ahmb | $2595.00 |
Frozen Mouse Embryo | FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(ACTA1-SMN)69Ahmb | $3373.50 |
Frozen Mouse Embryo | FVB.Cg-Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(ACTA1-SMN)69Ahmb | $3373.50 |
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