Background: Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans.
Results: In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137 miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137 miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD.
Conclusions: Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137 miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.
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http://dx.doi.org/10.1186/s13578-024-01268-8 | DOI Listing |
PLoS One
January 2025
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Clarifying the inceptive pathophysiology of hypertensive heart disease helps to impede the disease progression. Through coarctation of the infrarenal abdominal aorta (AA), we induced hypertension in minipigs and evaluated physiological reactions and morpho-functional changes of the heart. Moderate aortic coarctation was achieved with approximately 30 mmHg systolic pressure gradient in minipigs.
View Article and Find Full Text PDFFood Res Int
January 2025
Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint Gilles, France. Electronic address:
Despite the WHO recommendations in favor of breastfeeding, most infants receive infant formulas (IFs), which are complex matrices involving numerous ingredients and processing steps. Our aim was to understand the impact of the quality of the protein ingredient in IFs on gut microbiota and physiology, blood metabolites and brain gene expression. Three IFs were produced using whey proteins (WPs) from cheese whey (IF-A) or ideal whey (IFs-C and -D) and caseins, either in a micellar form (IFs-A and -C) or partly in a non-micellar form (IF-D).
View Article and Find Full Text PDFJ Otol
October 2024
The Institute of Audiology and Balance Science, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
Objective: This study aims to explore the expression patterns of cysteine string protein alpha (CSPα) and cysteine string protein beta (CSPβ) in the mammalian inner ear, with an emphasis on their temporal dynamics during the developmental stages of C57BL/6 mice.
Methods: We utilized immunofluorescence staining to assess the localization and distribution of CSPα and CSPβ within the inner ears of C57BL/6 mice and miniature pigs. Additionally, this method facilitated the investigation of their temporal expression profiles.
Biopharm Drug Dispos
January 2025
Bioavailability Research Project, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
Establishment of a suitable animal model to evaluate sustained release (SR) formulations is very important because it reduces the development time of SR formulations. Beagle dogs are often used to evaluate prototype formulations since they can be directly administered powder, such as drug substance. However, the physiological condition of dogs is very different to that of humans.
View Article and Find Full Text PDFZhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
December 2024
Endoscopy Center, Peking University People's Hospital, Beijing100044, China.
To establish a novel laryngopharyngeal reflux model in Bama minipigs excluding concurrent gastroesophageal reflux through endoscopic cricopharyngeal myotomy. Twelve 8-month-old male Bama minipigs were randomly assigned to three groups: Group 1 underwent cricopharyngeal myotomy alone, Group 2 underwent combined cricopharyngeal and lower esophageal sphincter myotomy, and Group 3 served as the control group. Following a one-week acclimatization period, the respective surgical procedures were performed.
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