AUTHOR=Yang Wan , Zuo Yiyi , Zhang Nuo , Wang Kangning , Zhang Runze , Chen Ziyi , He Qing 

TITLE=GNAS locus: bone related diseases and mouse models

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1255864

DOI=10.3389/fendo.2023.1255864

ISSN=1664-2392

ABSTRACT=GNAS is a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the GNAS gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone (PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the GNAS locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the GNAS locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases. transcripts originating from GNAS locus, such as A/B, XLas, and NESP55, share exons 2 through 13 with Gsα, but utilize their unique promoters and first exons.In most tissues, Gsα is transcribed from both paternal and maternal alleles. However, in specific tissues like renal proximal tubules, thyroid, ovaries, and pituitary, there is a preferential expression of the maternal allele. In contrast, A/B, XLas, and AS are paternally expressed due to methylation of their maternal promoters at CpG islands within differentially methylated regions (DMRs). While NESP55 is expressed by the maternal allele, its DMR is methylated on the paternal allele (3-6).