RGD Reference Report - Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality. - Rat Genome Database

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Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality.

Authors: Shiono, M  Kobayashi, T  Takahashi, R  Ueda, M  Ishioka, C  Hino, O 
Citation: Shiono M, etal., Sci Rep. 2014 Aug 4;4:5927. doi: 10.1038/srep05927.
RGD ID: 11568651
Pubmed: PMID:25088526   (View Abstract at PubMed)
PMCID: PMC5379989   (View Article at PubMed Central)
DOI: DOI:10.1038/srep05927   (Journal Full-text)

The Tsc2 product, tuberin, negatively regulates the mTOR pathway. We have exploited the Eker (Tsc2-mutant) rat system to analyse various Tsc2 mutations. Here, we focus on the N525S-Tsc2 variant (NSM), which is known to cause distinct symptoms in patients even though normal suppression of mTOR is observed. Unexpectedly, we were repeatedly unable to generate viable rats carrying the NSM transgene. Genotypic analysis revealed that most of the embryos carrying the transgene died around embryonic day after 14.5-similar to the stage of lethality observed for Eker homozygotes. Thus, the NSM transgene appeared to have a dominant lethal effect in our rat model. Further, no significant differences were observed for various signal transduction molecules in transiently expressed NSM cells compared to WT. These results indicate that a non-mTOR pathway, critical for embryogenesis, is being regulated by tuberin, providing a link between tuberin expression and the severity of Tsc2 mutation-related pathogenesis.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
embryonic lethality  IMP 11568651 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tsc2  (TSC complex subunit 2)


Additional Information