Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-PaschiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies.

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Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation

Nature Communications ◽

10.1038/s41467-019-13033-4 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 7

Author(s):

Julia Schewe ◽

Eric Seidel ◽

Sofia Forslund ◽

Lajos Marko ◽

Jörg Peters ◽

...

Keyword(s):

Blood Pressure ◽

Mouse Model ◽

Oscillatory Activity ◽

Type Ii ◽

Mild Form ◽

Familial Hyperaldosteronism ◽

Aldosterone Production ◽

Knockout Model ◽

Knockin Mouse

AbstractGain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2R180Q/+ mice, adrenal morphology is normal, but Cyp11b2 expression and plasma aldosterone levels are elevated. Male Clcn2R180Q/+ mice have increased aldosterone:renin ratios as well as elevated blood pressure levels. The counterpart knockout model (Clcn2−/−), in contrast, requires elevated renin levels to maintain normal aldosterone levels. Adrenal slices of Clcn2R180Q/+ mice show increased calcium oscillatory activity. Together, our work provides a knockin mouse model with a mild form of primary aldosteronism, likely due to increased chloride efflux and depolarization. We demonstrate a role of ClC-2 in normal aldosterone production beyond the observed pathophysiology.

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The miR-21 potential of serving as a biomarker for liver diseases in clinical practice

Biochemical Society Transactions ◽

10.1042/bst20200653 ◽

2020 ◽

Vol 48 (5) ◽

pp. 2295-2305

Author(s):

Jiawei Zhang ◽

Dandan Li ◽

Rui Zhang ◽

Peng Gao ◽

Rongxue Peng ◽

...

Keyword(s):

Clinical Practice ◽

Liver Diseases ◽

Hepatic Disease ◽

Noninvasive Detection ◽

Diagnosis And Prognosis ◽

Expected Performance ◽

Potential Biomarker ◽

Disease Condition ◽

Complex Regulatory Network

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.

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