These SMN2; Smn; PrP92-SMN mutant mice may be useful in 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) |
As described for SMA mice (see Stock No. 005024), mice homozygous for Smn1tm1Msd targeted mutation (Smn null allele) and human SMN2 transgene (SMN2 low copy line 89) 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 PrP-SMN transgene; with the mouse prion protein (PrP or Prnp) promoter directing full-length human SMN expression at high levels in neurons (with low expression in skeletal muscle and liver). When the PrP-SMN transgene is derived from PrP92-SMN founder mice, high SMN expression in spinal cord and brain is observed. Homozygous SMN2; Smn; Prp92-SMN mice are rescued from the severe SMA phenotype, have significantly increased lifespan (average of 210 days) and have normal lumbar motor neuron root counts. Homozygous SMN2; Smn; PrP92-SMN males are infertile, females are fertile but poor mothers, and both sexes exhibit necrotic tail development with about one-third of the normal length remaining around the time of weaning. These SMN2; Smn; PrP92-SMN mutant mice may be useful in neuromuscular studies including spinal muscular atrophy (SMA).
These SMN2; Smn; PrP92-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 PrP-SMN transgene was designed with the mouse prion protein gene (PrP or Prnp) promoter region and exon 1 and 2, full-length SMN cDNA (containing exons 1-8), and two SV40 polyA signals. This transgene was microinjected into fertilized FVB/N oocytes. Mice from founder line 92 (PrP92-SMN) were found to have 8-9 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).
These SMN2; Smn; PrP92-SMN mutant mice (heterozygous for the targeted mutation and homozygous for both transgenes) were maintained on a mixed genetic background (mostly FVB/N and C57BL/6) 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 92, Arthur H M Burghes |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | PrP92-SMN |
Gene Symbol and Name | Tg(Prnp-SMN)92Ahmb, transgene insertion 92, Arthur H M Burghes |
Gene Synonym(s) | |
Promoter | Prnp, prion protein, mouse, laboratory |
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 PrP-SMN transgene was designed with the mouse prion protein gene (PrP or Prnp) promoter region and exon 1 and 2, full-length SMN cDNA (containing exons 1-8), and two SV40 polyA signals. Mice from founder line 92 (PrP92-SMN) were found to have 8-9 copies of the transgene. |
When maintaining a live colony, mice heterozygous for the Smn1tm1Msd targeted mutation, homozygous for the SMN2 low copy line 89 transgene, and homozygous for the PrP92-SMN transgene are bred together. The donating investigator reports that mice homozygous for all three mutations are poor breeders (males infertile, females poor mothers). The SMN2 low copy line 89 transgene is reported to have a single copy (thus homozygotes have 2 copies). The PrP92-SMN transgene copy number should be monitored as the phenotype of SMA models may be greatly affected by copy number variations.
When using the STOCK Grm7Tg(SMN2)89Ahmb Smn1tm1Msd Tg(Prnp-SMN)92Ahmb/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008212 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Tg(SMN2)89Ahmb, Homozygous for Smn1<tm1Msd>, Homozygous for Tg(Prnp-SMN)92Ahmb |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Prnp-SMN)92Ahmb/J | $2595.00 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Prnp-SMN)92Ahmb/J | $2595.00 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Prnp-SMN)92Ahmb/J | $3373.50 |
Frozen Mouse Embryo | STOCK Grm7<Tg(SMN2)89Ahmb> Smn1<tm1Msd> Tg(Prnp-SMN)92Ahmb/J | $3373.50 |
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