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Published on: February 11, 2021
Assessment of intestinal status in MPLW515L mutant myeloproliferative neoplasms mice model
Shengyun Zhu1, Kairen Xu2, Shuyao Li2
1Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Hematology, Affliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cells, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Abstract:
The MPLW515L mutation is a prevalent genetic mutation in patients with myeloproliferative neoplasms (MPN), and utilizing this mutation in mice model can provide important insights into the disease. However, the relationship between intestinal homeostasis and MPN mice model remains elusive. In this study, we utilized a retroviral vector to transfect hematopoietic stem cells with the MPLW515L mutation, creating mutated MPN mice model to investigate their intestinal status. Our results revealed that the MPLW515L in MPN mice model aggravated inflammation in the intestines, decreased the levels of tight junction proteins and receptors for bacteria metabolites. Additionally, there was increased activation of the caspase1/IL-1β signaling pathway and a significant reduction in phos-p38 levels in the intestinal tissue in MPN mice. The MPLW515L mutation also led to up-expression of anti-microbial genes in the intestinal tract. Though the mutation had no impact on the alpha diversity and dominant bacterial taxa, it did influence the rare bacterial taxa/sub-communities and consequently impacted intestinal homeostasis. Our findings demonstrate the significance of MPLW515L mice model for studying MPN disease and highlight the mutation's influence on intestinal homeostasis, including inflammation, activation of the IL-1β signaling pathway, and the composition of gut microbial communities.
Insights
The MPLW515L mutation in myeloproliferative neoplasms (MPN) mice models causes intestinal inflammation and disrupts gut microbial communities. This research highlights the MPLW515L mice model
Area of Science:
- Hematology
- Gastroenterology
- Molecular Biology
Background:
- The MPLW515L mutation is common in myeloproliferative neoplasms (MPN).
- The impact of MPN on intestinal homeostasis is not well understood.
- MPN mouse models are crucial for studying disease mechanisms.
Purpose of the Study:
- To investigate the effects of the MPLW515L mutation on intestinal homeostasis in a mouse model.
- To elucidate the molecular and microbial changes in the intestine associated with MPN.
Main Methods:
- Hematopoietic stem cells were transfected with the MPLW515L mutation using a retroviral vector to create a mouse model.
- Intestinal tissues were analyzed for inflammation markers, tight junction proteins, and microbial composition.
- The caspase1/IL-1β signaling pathway and phos-p38 levels were assessed.
Main Results:
- MPLW515L MPN mice exhibited increased intestinal inflammation.
- Levels of tight junction proteins and bacterial metabolite receptors were decreased.
- The caspase1/IL-1β pathway was activated, while phos-p38 levels decreased.
- Anti-microbial gene expression was upregulated.
- Gut microbial communities were altered, particularly rare taxa, impacting homeostasis.
Conclusions:
- The MPLW515L mutation significantly disrupts intestinal homeostasis in MPN mice.
- This mouse model is valuable for studying MPN pathogenesis and its gastrointestinal manifestations.
- Findings reveal key molecular pathways and microbial shifts contributing to MPN-associated intestinal dysfunction.
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