Animal models and experimental medicine最新文献

The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation, endothelial cell dysfunction, and thrombosis, which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are many laboratory models of active SARS-CoV-2 infection in mice, reflecting an acute lung injury in an otherwise healthy animal, but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease. The monocrotaline (MCT)–treated rat is a widely used laboratory model of pulmonary hypertension (PH). Not often discussed, however, are the observed changes in inflammation, edema, fibrosis, and microthrombosis in the lung prior to PH. At the cellular level, there is loss of pneumocytes and endotheliopathy, and at the molecular level the MCT rat lung is characterized by a pro-inflammatory cytokine profile, namely elevated interleukin 6, transforming growth factor β and tumor necrosis factor, M1 macrophage phenotype, and dysregulation of the angiotensin converting enzyme (ACE)/ACE2 balance. The systems-level pathophysiology of the MCT-treated rat includes progressive cardiopulmonary dysfunction. The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology, but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung. The MCT-treated rat lung as a model of the COVID-19 lung may provide an in-depth understanding of the factors that drive the lung to more severe pathology, treatments that benefit lung recovery, or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.

Background: SEC16A is a pivotal protein that facilitates the transport of proteins from the endoplasmic reticulum to the Golgi apparatus. Utilizing the protein structure function database, a potentially pathogenic mutation site (NM_014866.1: c.4606C>G(p.L1536V)) was pinpointed within the conserved central core region of the human SEC16A protein, a component integral to the COPII complex assembly.

Methods: Leveraging information on human gene mutations and aligning human and mouse protein amino acid sequences, the Sec16aL1551V/L1551V mouse model was successfully developed using CRISPR/Cas9 technology.

Results: Two behavioral experiments, namely novel object recognition and cued fear conditioning, revealed that Sec16aL1551V/L1551V mice demonstrated a phenotype of neurological impairment, evidenced by diminished abilities in learning and memory. Furthermore, while undergoing tail suspension, the Sec16aL1551V/L1551V mice displayed a distinctive limb clasping behavior, a characteristic typically associated with mouse models of chronic neurodegenerative diseases.

Conclusion: The Sec16aL1551V/L1551V mouse model developed in this study providing a powerful tool for better understanding of the pathogenic mechanisms of Sec16a gene mutations in brain dysfunction diseases.

MicroRNAs (miRNAs) are crucial in diverse biological processes. In recent years, extensive research has significantly advanced our understanding of miRNA biogenesis, function, and its implications in various biological processes and diseases. In development, miRNAs precisely regulate gene expression to ensure proper organismal growth. miRNAs serve as essential modulators of cell proliferation and differentiation, thereby determining cell fate. Regarding the regulation of apoptosis, miRNAs play a significant role in controlling programmed cell death. Moreover, in metabolism, miRNAs are involved in modulating various pathways. This review examines the latest advancements in miRNA research, encompassing their biogenesis, functional roles, and involvement in various biological processes and diseases. A specific emphasis is placed on the roles of miRNAs in development, cell proliferation, apoptosis, and metabolic regulation. Additionally, cutting-edge technologies were discussed for the potential therapeutic applications of miRNA-based strategies.

Accurate macaque paternity identification is of great significance in various fields, yet relevant research remains scarce. Our study aimed to screen effective microsatellite markers for macaque paternity testing. Initially, 300 microsatellite markers were randomly selected from the genome of the crab-eating macaque (Macaca fascicularis), and 12 highly polymorphic tetra-nucleotide repeat markers were identified. These markers' genetic parameters and exclusion probabilities in both crab-eating and rhesus macaque (Macaca mulatta) populations were calculated, meeting the paternity testing requirements for both species. To validate the markers, 16 crab-eating macaque and 10 rhesus macaque families with known pedigrees were randomly chosen for testing. The genotypes of the 12 markers in the macaques' offspring could be traced back to their parents, confirming the accuracy and applicability of the marker combination for paternity identification in both macaque species.

Experimental mice play a critical role in biomedical research. The phenotype and application of different substrains vary due to genetic differentiation and variation. To ensure validity and reliability of results, it is imperative to adhere to standardized experiments and controls. This paper objectively reviews the origin, differentiation, and phenotypic and genetic differences between the C57BL/6 and BALB/c mouse substrains. Furthermore, an optimal selection strategy is proposed based on the genetic quality control technology to facilitate the precise application of these two mouse substrains.