Mice that are homozygous for the Smn1 targeted mutation have an embryonic lethal phenotype, failing to survive past embryonic day 6.5. Heterozygotes are viable and fertile. This knock-out line is the control for FVB.Cg-Smn1tm1Hung Tg(SMN2)2Hung/J (Stock No. 005058).
This targeted mutant allele was generated by disrupting exon 7 with a vector containing neomycin resistance and herpes simplex virus thymidine kinase genes. This construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric animals obtained. Chimeric animals were crossed to C57BL/6 for more than 5 generations. The mice were crossed to a transgenic line on the FVB/N genetic background, and then backcrossed to FVB/N for 5 generations. Mice were then bred to remove the transgene to generate this single mutant line.
|Allele Name||targeted mutation 1, Hung Li|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Smn-; Smndelta 7|
|Gene Symbol and Name||Smn1, survival motor neuron 1|
|Strain of Origin||129P2/OlaHsd|
|General Note||Homozygous mutant mice died during the peri-implantation stage. |
In contrast, homozygous mutant mice carrying Tg(SMN2)1Hung display pathological changes in the spinal cord and skeletal muscles similar to those of patients with proximal spinal muscular atrophy (SMA). Some of these mice do not develop hairy fur, and die before postnatal day 10. Others exhibit poor activity and variable symptoms, and die at approximately 2-4 weeks. A third group of these mice survive to adulthood and are fertile, but have short enlarged tails. The variable severity of the pathological changes in these mice correlates with transgene copy number and the amount of protein that contains the region encoded by exon 7.
|Molecular Note||Exon 7 was replaced with an HPRT cassette via homologous recombination. Homozygous embryos were detected at E3.5 but not after E6.5.|
|Mutations Made By|| |
Hung Li, Institute of Molecular Biology
The Jackson Laboratory Stock No. 031679 is routinely maintained by breeding heterozygous mice to wildtype siblings, or to FVB/NJ inbred mice (Stock No. 001800). Mice homozygous for the Smn1tm1Hung knock-out allele are not viable.
When using the Smn delta 7 mouse strain in a publication, please cite the originating article(s) and include JAX stock #031678 in your Materials and Methods section.