相关实验视频

Updated: May 9, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

转录组分析显示,在自发性猫类甲状腺功能增强症中激活G_sα突变的关键作用

Thomas K Hiron^1,2, Joana Aguiar^1,3, Jonathan M Williams⁴

¹Department of Clinical Science and Services, The Royal Veterinary College, Hertfordshire, AL9 7TA, UK.

Scientific reports

|November 20, 2024

概括

激活Gsα的突变是猫类甲状腺功能障碍症 (FHT) 的关键驱动因素,导致过度的甲状腺激素产生,独立于TSH. 这一发现揭示了FHT的新治疗标途径.

科学领域:

兽医医学兽医医学兽医医学
分子生物学分子生物学
内分泌学在内分泌学.

背景情况:

猫类甲状腺功能障碍 (FHT) 是老猫群中常见的内分泌疾病,其特征是甲状腺激素升高而没有甲状腺刺激激素 (TSH).
FHT背后的分子机制尚未完全理解,但它与人类有毒的多节有相似之处,与TSH受体 (TSHR) 和Gsα基因的突变有关.

研究的目的:

通过分析基因表达和识别猫类甲状腺组织中的遗传变异来研究FHT的分子病变.
确定TSHR和Gsα突变在猫的TSH独立甲状腺功能障碍的发展中的作用.

主要方法:

甲状腺组织的RNA-sequencing (RNA-seq) 转录组分析,来自甲状腺功能高和甲状腺功能良好的猫.
使用RNA-seq数据检测和描述TSHR和Gsα基因中的误解变异.
鉴定Gsα突变对cAMP产生的功能影响的体外评估.

主要成果:

在FHT中发现了差异表达的基因和TSHR下游的失调路径.
在猫类甲状腺组织中检测到TSHR和Gsα的获得误解变异,但在生殖基因DNA中没有.
所有晚期FHT病例都表现出Gsα至少一个误解变异,这在体外明显增加了cAMP的产生,表明构成性激活.

结论:

构成性TSHR信号的激活,主要是通过获得的Gsα突变,是FHT中TSH独立甲状腺激素过度产生的核心.
这些发现确定了一种新的治疗向途径,用于治疗猫类甲状腺功能障碍.

更多相关视频

High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model

High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model

Published on: October 11, 2022

Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model

Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model

Published on: October 6, 2023

相关概念视频

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...

Hyperthyroidism I: Introduction

Hyperthyroidism I: Introduction

Hyperthyroidism is a type of thyrotoxicosis characterized by the thyroid gland's overproduction of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). This hormone excess increases the basal metabolic rate and enhances sensitivity to catecholamines.DiagnosisDiagnosis is based on clinical features and biochemical testing. It typically shows suppressed thyroid-stimulating hormone (TSH) levels below 0.4 mIU/L, with elevated free T3 and/or T4. Additional tests, including thyroid...

Hyperthyroidism II: Pathophysiology

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...

Graves Disease II: Pathophysiology

Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...