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| Status |
Public on Mar 27, 2024 |
| Title |
Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression [baseline] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human-specific changes in specific Siglecs is one of the reasons put forth as molecular mechanisms that could explain human proneness to developing cancers. The SIGLEC12 gene, which encodes the Siglec-XII protein mainly found on epithelial cells, has a fixed homozygous missense mutation in a critical arginine renders unable to recognize its natural ligand. Additionally, the gene harbors a polymorphic frameshift mutation that eliminates expression of the full-length protein in most humans. We hypothesized that dysfunctional Siglec-XII is involved in cancer progression in humans' epithelia. Here we report that the transgenic conditional expression of human Siglec-XII in mouse intestinal epithelia did not by itself cause carcinomas and RNA sequencing of the colons at baseline derived a gene signature without differentially expressed genes (DEGs) between controls (Villin1-Cre-ER(T2)) and Siglec-XII-expressing mice
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| Overall design |
To investigate the impact of the expression of human SIGLEC12 in mouse epithelia, we developed a knock-in mouse model that allows its conditional expression only in the villi and crypts of the small and large intestine (SIGLEC12-Villin1-Cre-ERT). SIGLEC12 knock in mice (SIGLEC12-Villin1-Cre-ERT) and controls (Villin1-Cre-ERT) received 5 days treatment (10 mg/ml) with tamoxifen, to induce SIGLEC12 expression. After 7 days of the last tamoxifen administration mice were sacrificed, colons were harvested. We then performed gene expression profiling analysis using data obtained from RNA-seq of three mice for each condition.
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| Contributor(s) |
Varki A, Ghosh P |
| Citation(s) |
38990656 |
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| Submission date |
Mar 20, 2024 |
| Last update date |
Sep 27, 2024 |
| Contact name |
Pradipta Ghosh |
| E-mail(s) |
prghosh@ucsd.edu
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| Organization name |
University of California San Diego
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| Department |
Departments of Medicine and Cellular and Molecular Medicine
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| Street address |
9500 Gilman Drive (MC 0651)
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| City |
La Jolla, CA 92093 |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE262088 |
Human-Specific Elimination of Epithelial Siglec-XII Suppresses the Risk of CRC Initiation and Progression |
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| Relations |
| BioProject |
PRJNA1090163 |
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