These transgenic mice express the constitutively active point mutation, SmoA1, of the mouse smoothened homolog (Drosophila) (Smo) gene, under the control of the mouse neurogenic differentiation 2 (Neurod2) promoter, with transgene expression specific to cerebellar granule cells. Homozygous mice show an increased medulloblastoma incidence. This transgenic mouse strain may be useful in studies of medulloblastoma and metastasis.
James M Olson, Fred Hutchinson Cancer Research Center
Genetic Background | Generation |
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Allele Type |
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Transgenic (Constitutively active, Inserted expressed sequence) |
These Smo/Smo transgenic mice express the constitutively active point mutation, SmoA1, of the mouse smoothened homolog (Drosophila) (Smo) gene, under the control of the 1kb mouse neurogenic differentiation 2 (Neurod2) promoter. Transgene expression is specific to cerebellar granule cells, as observed by His tag staining. Tumor incidence in mice homozygous for the transgene is 85% by one month of age and 94% by two months of age, with an average age of onset of related traits being four months. Traits associated with advanced tumors include enlarged posterior fossa, and/or tilted head, and hunched posture. Weight loss and an ungroomed appearance are also common. The disease progresses to leptomeningeal metastasis of the brain and spine. Once clinical symptoms are noted, survival is one to two weeks. This mutant mouse strain may be useful in studies of medulloblastoma and metastasis.
The ND2:SmoA1 transgene containing the entire mouse smoothened homolog (Drosophila) (Smo) gene, with the constitutively active point mutation SmoA1, driven by the 1kb mouse neurogenic differentiation 2 (Neurod2) promoter was microinjected into C57BL/6. Founder line A1.199 was subsequently established. The hemizygote animals were were backcrossed to both C57BL/6J and C57BL/6NCrl for an unknown number of generations. The hemizygotes were then intercrossed to produce homozygotes, referred to as Smo/Smo mice. The mice were maintained as homozygotes for more than 10 generations before arriving at The Jackson Laboratory. The transgene insertion site has been mapped by plasmid probe to Chromosome 14 at band qC1.
Expressed Gene | Smo, smoothened, frizzled class receptor, mouse, laboratory |
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Site of Expression |
Allele Name | transgene insertion 199, James M Olson |
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Allele Type | Transgenic (Constitutively active, Inserted expressed sequence) |
Allele Synonym(s) | ND2:SmoA1; SmoA1; SmoA1:199 |
Gene Symbol and Name | Tg(Neurod2-Smo*A1)199Jols, transgene insertion 199, James M Olson |
Gene Synonym(s) | |
Promoter | Neurod2, neurogenic differentiation 2, mouse, laboratory |
Expressed Gene | Smo, smoothened, frizzled class receptor, mouse, laboratory |
Strain of Origin | C57BL/6 |
Chromosome | 14 |
Molecular Note | The ND2:SmoA1 transgene contains the entire mouse smoothened homolog (Drosophila) Smo gene, with the constitutively active point mutation SmoA1 (W539L), driven by the 1kb mouse neurogenic differentiation 2 (Neurod2) promoter. Several lines were generated (lines 199, 193, 234, 255 and 201) with varying levels of expression (30-, 45-, 36-, 2- and 3-fold, respectively, relative to wild0type expression). |
When maintaining a live colony, these mice can be bred as homozygotes. However, subclinical tumor incidence in homozygotes is 85% by 1 month of age and 94% by 2 months of age. The average age of onset of clinical tumor symptoms at four months. Once clinical symptoms are noted, survival is 1-2 weeks. It is not uncommon for female breeders to develop a tumor while pregnant or nursing. When this occurs, pups are fostered into another age-matched litter. The Donating Investigator reports that some breeder pairs will produce only one litter while most will have three litters before tumor formation.
When using the ND2:SmoA1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #008831 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or non carrier for Tg(Neurod2-Smo*A1)199Jols/ |
Frozen Mouse Embryo | C57BL/6-Tg(Neurod2-Smo*A1)199Jols/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Tg(Neurod2-Smo*A1)199Jols/J | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Tg(Neurod2-Smo*A1)199Jols/J | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Tg(Neurod2-Smo*A1)199Jols/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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