Project description:Developing cost-effective and disease-relevant animal models is essential for advancing biomedical research into human disorders. This study investigates the feasibility of a pig model for autism spectrum disorder (ASD) using embryonic exposure to valproic acid (VPA), an antiepileptic drug known to increase ASD risk. We established experimental paradigms to assess the behavioral characteristics of these pig models. Administration of VPA to Bama miniature pigs (Sus scrofa domestica) during critical embryonic stages resulted in abnormal gait, increased anxiety levels, reduced learning capabilities, and altered social patterns, while largely preserving social preference of treated piglets. Notably, we detected significant neuroanatomical changes in cortical regions associated with ASD in the VPA-treated pigs, including cortical malformation, increased neuronal soma size, decreased dendritic complexity, and reduced dendritic spine maturation. Transcriptome analysis of the prefrontal cortex of VPA-treated pigs further revealed substantial alterations in the expression of genes linked to ASD, especially genes of the dopamine signaling pathway, highlighting the model’s relevance and potential for shedding light on ASD’s underlying neuropathological and molecular mechanisms. These findings suggest that pig models could serve as a promising alternative to traditional rodent models and provide an ethical substitute for using primates in the translational research of neurodevelopmental disorders.
Project description:Miniature pig is a useful animal model to clarify the vital reaction and the molecular mechanisms. However, physiclogical response of pig model to sodium azide (AZIDE) stress is not reveal. To establishment of large animal model for evaluate toxic stress, whole blood of miniature pig were assessed with genomics.
Project description:Miniature pig is a useful animal model to clarify the vital reaction and the molecular mechanisms. However, physiclogical response of pig model to sodium azide (AZIDE) stress is not reveal. To establishment of large animal model for evaluate toxic stress, whole blood of miniature pig were assessed with genomics. 7 month old clawn miniature pigs were fed AZIDE feeding. AZIDE dose of 300µg/kg, one hundredth of LD50 was given orally to the miniature pigs. Whole blood gene expression was measured at 0h, 6h and 24h after feeding.
Project description:Large animal models for Duchenne muscular dystrophy (DMD) are indispensible for preclinical evaluation of novel diagnostic procedures and treatment strategies. To evaluate functional consequences of Duchenne muscular dystrophy (DMD) in skeletal muscle and myocardium, we used a new genetically engineered dystrophin KO pig model displaying hallmarks of human DMD. Heart and skeletal muscle tissue samples of DMD pigs and wild-type (WT) controls at three different ages were analyzed by label-free proteomics.
Project description:Autism spectrum disorder (ASD) affects gene expression in early postnatal development. We used valproic acid (VPA)-induced ASD model marmosets. Gene expression in VPA-exposed and unexposed (UE) marmosets were analyzed at 0, 3 and 6 months (M). We revealed three groups of differentially expressed genes based on the temporal patterns of modulation.
Project description:To study the development of pig facial skin after birth, we use the facial skin tissues of healthy Chenghua sows as experimental materials. we then performed gene expression profiling analysis using data obtained from RNA-seq of pig facial skin tissues at four time points.
Project description:Advanced paternal age has been shown to be a significant risk factor for neurodevelopmental psychiatric disorders, particularly autism. We have recently shown that mice conceived by old fathers display behavioral abnormalities which resemble key diagnostic symptoms of human autism. De novo mutations and epigenetic alterations increase in the male germ line during ageing and are thought to mediate the effect of paternal age on occurrence of diseases occurrence. Because the placenta carry a predominantly fetal genetic background, age-related mutagenesis and epigenetic errors might negatively influence placental physiology and in turn perturb fetal brain development. Here, we examined the impact of paternal age on placental mRNA transcriptome. This work was supported by Programme FP7-KBBE-2012.1.3-04, GA no. 312097 Acronym: FECUND, to GEP; MIUR/CNR, Programme FIRB. GA n. B81J12002520001 Acronym: GenHome, to PL. This study was also partially financed by the IGAB PAS project (S.III.1.3), Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants N N519 657940 and N N311 604938. We compared gene expression patterns of mouse placentas harvested from either advanced paternal age model (APA) of autism or control animals. We included 2 comparisons: 1) placenta of female APA vs placenta of female control; 2) placenta of male APA vs placenta of male control. Each comparison was composed of 3 biological replicates. To minimize family bias, poolings contained at most one placenta per sex from each dam to a minimum of one and a maximum of three placentas per group/sex.