Transcriptomic analysis of first molars in a mouse model of Loeys-Dietz Syndrome Type II harboring a G357W mutation in the Tgfbr2 gene

Loeys Dietz Syndrome (LDS) is a connective tissue disorder caused by mutations along the TGF-beta signaling pathway and characterized by severe aortic aneurysm and craniofacial anomalies. Patients with LDS Type II (LDS2), caused by mutations in the TGFBR2 gene also exhibit enamel defects. A mouse model for LDS2, harboring a G357W mutation in the Tgfbr2 gene, recapitulates the cardiovascular, craniofacial and dental phenotype of the disease. This transcriptomic analysis aimed at identifying genes that are differentially regulated in first molars of Tgfbr2-G357W/+ mice at postnatal day 5 and 11. Total RNA was extracted from enamel organs from Tgfbr2-G357W/+ mice (LDSR2, KI) and Tgfbr2-+/+ wild-type littermates (WT). Total RNA from first mandibular molars at P5 and P11 from five Tgfbr2-G357W/+ mice (LDSR2, Het) and eight Tgfbr2-+/+ wild-type littermates (WT) was collected for bulk RNA-seq analysis.洛伊斯·迪茨综合征（Loeys Dietz Syndrome, LDS）是一类由转化生长因子β（TGF-beta）信号通路突变引发的结缔组织疾病，以严重主动脉瘤与颅面畸形为核心特征。由人转化生长因子β受体2（TGFBR2）基因突变导致的LDS II型（LDS2）患者，还可出现牙釉质发育缺陷。本研究构建的LDS2小鼠模型，在小鼠Tgfbr2基因中携带G357W突变，可重现该疾病的心血管、颅面及牙齿表型。本次转录组分析旨在鉴定出生后第5天（P5）与第11天（P11）的Tgfbr2-G357W/+小鼠第一磨牙中差异调控的基因。研究人员从Tgfbr2-G357W/+小鼠（LDSR2，KI）与Tgfbr2-+/+野生型同窝对照（WT）的牙釉质器官中提取总RNA，并收集了5只Tgfbr2-G357W/+小鼠（LDSR2，Het）以及8只野生型同窝对照在P5与P11阶段的下颌第一磨牙总RNA，用于批量RNA测序（bulk RNA-seq）分析。