Larsen Knud, Momeni Jamal, Farajzadeh Leila, Callesen Henrik, Bendixen Christian
Department of Molecular Biology and Genetics, Aarhus University, Blichers Allé 20, DK-8830 Tjele, Denmark.
Department of Animal Science, Aarhus University, Blichers Allé 20, DK-8830 Tjele, Denmark.
Biochim Open. 2016 Jul 19;3:26-39. doi: 10.1016/j.biopen.2016.07.001. eCollection 2016 Dec.
Orphan receptor NURR1 (also termed NR4A2) belongs to the nuclear receptor superfamily and functions as a regulatory factor of differentiation, migration, maturation and maintenance of mesencephalic dopaminergic neurons. NURR1 plays an important role in nigrostriatal dopamine neuron development and is therefore implicated in the pathogenesis of neurodegenerative diseases linked to the dopamine system of the midbrain. Here we report the isolation and characterization of porcine cDNA. The cDNA was RT-PCR cloned using NURR1-specific oligonucleotide primers derived from sequences. The porcine cDNA encodes a polypeptide of 598 amino acids, displaying a very high similarity with bovine, human and mouse (99%) NURR1 protein. Expression analysis revealed a differential mRNA expression in various organs and tissues. transcripts could be detected as early as at 60 days of embryo development in different brain tissues. A significant increase in transcript in the cerebellum and a decrease in transcript in the basal ganglia was observed during embryo development. The porcine gene was mapped to chromosome 15. Two missense mutations were found in exon 3, the first coding exon of . Methylation analysis of the porcine gene body revealed a high methylation degree in brain tissue, whereas methylation of the promoter was very low. A decrease in DNA methylation in a discrete region of the promoter was observed in pig frontal cortex during pig embryo development. This observation correlated with an increase in transcripts. Therefore, methylation might be a determinant of expression at certain time points in embryo development.
孤儿受体NURR1（也称为NR4A2）属于核受体超家族，作为中脑多巴胺能神经元分化、迁移、成熟和维持的调节因子发挥作用。NURR1在黑质纹状体多巴胺神经元发育中起重要作用，因此与中脑多巴胺系统相关的神经退行性疾病的发病机制有关。在此，我们报告猪cDNA的分离和特征。该cDNA是使用源自序列的NURR1特异性寡核苷酸引物通过RT-PCR克隆的。猪cDNA编码一个由598个氨基酸组成的多肽，与牛、人和小鼠（99%）的NURR1蛋白具有非常高的相似性。表达分析揭示了在各种器官和组织中mRNA表达存在差异。早在胚胎发育60天时，就能在不同脑组织中检测到转录本。在胚胎发育过程中，观察到小脑中转录本显著增加，而基底神经节中转录本减少。猪基因被定位到15号染色体。在外显子3（的第一个编码外显子）中发现了两个错义突变。猪基因体的甲基化分析显示脑组织中甲基化程度很高，而启动子的甲基化程度非常低。在猪胚胎发育过程中，观察到猪额叶皮质中启动子一个离散区域的DNA甲基化减少。这一观察结果与转录本增加相关。因此，甲基化可能是胚胎发育特定时间点表达的一个决定因素。
