Abstract LB-147: Characterization of a Kaiso overexpressing transgenic mouse model
Bibliographic record
Abstract
Abstract Introduction: The WNT signaling pathway plays critical roles during embryogenesis and maintaining homeostasis of adult tissues. However constitutive WNT signaling leads to tumorigenesis. Upon activation of the WNT pathway, the main downstream effector of the WNT pathway, ß-catenin, stabilizes and translocates to the nucleus where it activates transcription of WNT target genes. Recently, our lab along with others identified the novel transcription factor Kaiso as a negative regulator of WNT target genes in mammalian cell lines and Xenopus models. However a study using a Kaiso depleted mouse model implicated Kaiso as a positive regulator of WNT signaling. Kaiso is a member of the BTB/POZ (broad-complex, tramtrack and bric-à-brac/poxvirus and zinc finger) protein family. The goal of this study is to elucidate the role of Kaiso in WNT signaling using the ApcMin/+ mouse model of intestinal cancer. Methodology: To assess the role of Kaiso in colon cancer in vivo, Kaiso overexpressing transgenic mice were created (KaisoTg). Targeted overexpression of Kaiso in KaisoTg mice was obtained by pronuclear injection of Kaiso cDNA under the control of the intestine-specific villin promoter. Reverse transcription PCR (RT-PCR) and Western Blot analyses were used to determine tissue specific Kaiso overexpression in KaisoTg mice. Immunohistochemisty (IHC) was performed on mouse intestinal tissues to examine the subcellular localization of Kaiso and assess developmental defects. KaisoTg mice were then mated with APCMin/+ mice models of intestinal cancer that develop polyps in the small intestine due to constitutively active -catenin. KaisoTg-APCMin/+ mice were examined for gross morphological phenotypes and IHC was performed on mouse intestinal tissues for Kaiso and other WNT target genes (e.g. cyclin D1) to elucidate the effects of Kaiso on the WNT pathway. Results: Western Blot analysis revealed high, moderate and low levels of Kaiso overexpression in three founder lines of the KaisoTg mice. RT-PCR analysis showed Kaiso overexpression limited to villin positive tissues including kidney, small and large intestines. IHC analysis of KaisoTg tissues showed no gross morphological differences compared to non-transgenic mice. However KaisoTg-APCMin/+ displayed decreased body size and weight, and had decreased life span when compared to the parentals (i.e. KaisoTg and APCmin/+). IHC analysis of KaisoTg-APCMin/+ mouse intestines revealed increased polyp numbers with Kaiso staining concentrated near the basal surface of the polyps. These data support Kaiso's potential role as an oncogene in mouse intestinal tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-147.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".