Tsc2+/- mice are useful in studying Tuberous sclerosis. In addition, the mTOR hyperactivation exhibited by Tsc2+/- mice causes impaired basal neuronal autophagy, resulting in autism spectrum disorder (ASD)-like basal dendritic spine pathology and social recognition/interaction deficits.
David J. Kwiatkowski, Brigham and Women's Hospital
Exon 2 of the tuberous sclerosis 2 gene (Tsc2) has been replaced by a neo cassette, abolishing gene expression. TSC2 is a putative tumor supressor. Mutation of TSC2 have been associated with the onset of tuberous sclerosis complex (TSC) which is characterized by the formation of non-malignant tumors in many different organs. Heterozygous (Tsc2+/-) mice are viable and fertile. Homozygous (Tsc2-/-) mice have an embryonic lethal phenotype, failing to develop past embryonic days 9.5 to 12.5 due to hepatic hypoplasia. Cultured neuroepithelial progenitor cells isolated from embryonic day 10.5 embryos display abnormal growth and differentiation. All heterozygotes develop multiple bilateral renal cystadenomas by 12-15 months of age. By 15 months, about half develop liver hemangiomas (more common in females than in males). Less than 10% develop extremity angiosarcomas or renal carcinoma. Little or no gene product (protein) is detected by Western blot in renal cystadenomas. PCR analysis reveals loss of the wildtype allele in about 30% of lesions. Phenotype variability is dependent on genetic background.
Tsc2 haploinsufficiency causes mTOR hyperactivation: the subsequent autophagy inhibition results in autism spectrum disorder (ASD)-like basal dendritic spine pathology and social recognition/interaction deficits. Rapamycin treatment rescues the dendritic spine pruning defect and social abnormalities. Tsc2+/- mice do not exhibit stereotyped/repetitive behavior, motor defects or anxiety-like behavior.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2 of the tuberous sclerosis 2 locus on chromosome 17. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. Heterozygotes were then intercrossed.
|Allele Name||targeted mutation 1, David J Kwiatkowski|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, David J Kwiatkowski; Tsc2tm1Djk|
|Gene Symbol and Name||Tsc2, tuberous sclerosis 2|
|Gene Synonym(s)||tuberin; Nafld; LAM; PPP1R160; TSC4; Rc; tuberous sclerosis 2|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin cassette was inserted into the second coding exon of the gene.|
|Mutations Made By|| |
David Kwiatkowski, Brigham and Women's Hospital
When maintaining a live colony, heterozygous mice may be bred together or to wildtype mice from the colony. Homozygotes have an embryonic lethal phenotype. The expected coat color is Black.
When using the B6;129S4-Tsc2tm1Djk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004686 in your Materials and Methods section.
|Heterozygous or wildtype for Tsc2<tm1Djk>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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