Mice that are homozygous for both the Smn1tm1Msd allele and the Tg(SMN2)11Tro transgene (SMN2, survival of motor neuron 2, centromeric, human) exhibit a very severe phenotype with survival ranging from hours up to 7 days after birth. This mutant mouse strain may be useful in neuromuscular studies involving Spinal Muscular Atrophy (SMA).
Thierry Bordet, TROPHOS
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Reporter, Null/Knockout) | Smn1 | survival motor neuron 1 |
Allele Type |
---|
Transgenic (Inserted expressed sequence, Humanized sequence) |
Mice that are homozygous for both the Smn1tm1Msd allele and SMN2 (survival of motor neuron 2, centromeric, human) transgene, founder line 11, exhibit a very severe phenotype with survival ranging from hours up to 7 days after birth. Mice that die at or shortly after birth are slightly smaller than normal littermates. Mice that survive for several days are indistinguishable from normal littermates in the first 48 hours, after which they exhibit diminished weight gain. Mice hemizygous for the transgene and homozygous for the targeted mutation display an embryonic lethal phenotype. Mice that are heterozygous for the Smn1tm1Msd allele and homozygous for the SMN2 transgene are viable, fertile and do not exhibit neuropathy. Mice homozygous for the transgene (and wildtype at the Smn1 locus) do not exhibit an SMA-like phenotype. This mutant mouse strain may be useful in neuromuscular studies involving Spinal Muscular Atrophy (SMA).
These double mutant mice were generated by crossing Tg(SMN2)11Tro transgenic mice with Smn1tm1Msd targeted mutant mice.
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 Smn 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 Donating Investigator reports that the Tg(SMN2)11Tro has been localized on chromosome 18. Mice hemizygous for the Tg(SMN2)11Tro transgene have 1 copy of the transgene.
The SMN2 transgene was created at Trophos (Marseilles, France). A 35.5 kb Ba mHI 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 11 were established and then mated to mice heterozygous for the Smn1tm1Msd allele. The double mutant mice were then backcrossed to C57BL/6N for at least 15 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating.
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 |
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 11, Thierry Bordet |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | SMN2(N11) |
Gene Symbol and Name | Tg(SMN2)11Tro, transgene insertion 11, Thierry Bordet |
Gene Synonym(s) | |
Promoter | SMN2, survival of motor neuron 2, centromeric, human |
Expressed Gene | SMN2, survival of motor neuron 2, centromeric, human |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | A 35.5 kb Ba mHI 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 11, which contains 1 copy of the transgene, were established. |
When maintaining a live colony, mice that are homozygous for the SMN2 transgene and heterozygous for the Smn1tm1Msd allele are bred with mice that are homozygous for the SMN2 transgene and wildtype at the Smn1 locus.
When using the B6.Cg-Tg(SMN2)11Tro Smn1tm1Msd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008629 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous for Tg(SMN2)11Tro, Heterozygous or wildtype for Smn1<tm1Msd> |
Frozen Mouse Embryo | B6.Cg-Tg(SMN2)11Tro Smn1<tm1Msd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(SMN2)11Tro Smn1<tm1Msd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(SMN2)11Tro Smn1<tm1Msd>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Tg(SMN2)11Tro Smn1<tm1Msd>/J Frozen Embryo | $3373.50 |
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