Related Experiment Video
Updated: Aug 7, 2025
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Feasibility analysis of ACTH adenoma model in USP8-/- mice
1Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. lijialika@163.com.
Introduction:
Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary tumours (35% to 60%) present with somatic mutations in the USP8 gene. USP8 mutations lead to enhanced deubiquitination of the epidermal growth factor receptor (EGFR) and result in an imbalance in EGFR signalling, accompanied by excessive activation of ACTH production and cell growth. USP8 emerged as a novel and exciting candidate gene for Cushing's disease.
Material And Methods:
In this study, USP8 mutant mouse models (USP8+/- and USP8-/-) were established, their phenotypes were analysed and identified, biochemical indexes were detected, pituitary and adrenal tissue specimens were taken for HE staining and immunohistochemical identification of hormones, and the differences between the 2 groups of mutant mice and wild type mice were analysed and compared.
Results:
Compared with the control group (wild type), immunofluorescence assay results for USP8+/- mice and USP8-/- mice showed increased pituitary ACTH expression, which was statistically different (p < 0.05), and there were no significant differences in body weight, plasma ACTH, 24-hour urinary free cortisol, and immunohistochemical results. Higher blood glucose in USP8-/- mice than in USP8+/+ mice was observed. The heart rates of USP8-/- mice were higher than those of USP8+/- mice and USP8+/+ mice. HE staining and tissue fibre staining were done, and no significant pathological changes were seen in the 3 groups of pituitary and adrenal tissues.
Conclusion:
USP8 knockout mice have the potential to form an animal model of ACTH adenoma.
Insights
USP8 gene mutations are linked to ACTH-secreting pituitary tumors. USP8 knockout mice exhibit increased pituitary ACTH, suggesting their potential as an animal model for ACTH adenoma.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in the USP8 gene are found in 35%-60% of adrenocorticotropic hormone (ACTH)-secreting pituitary tumors.
- USP8 mutations disrupt epidermal growth factor receptor (EGFR) deubiquitination, leading to aberrant EGFR signaling, excessive ACTH production, and cell growth.
- USP8 is identified as a key gene associated with Cushing's disease.
Purpose of the Study:
- To investigate the role of USP8 in ACTH adenoma development.
- To establish and characterize USP8 mutant mouse models for studying pituitary tumor formation.
Main Methods:
- Generation and analysis of USP8 mutant mouse models (USP8+/- and USP8-/-).
- Phenotypic analysis, biochemical index detection, and pituitary/adrenal tissue examination (HE staining, immunohistochemistry).
- Comparison of mutant mice with wild-type counterparts.
Main Results:
- USP8 mutant mice (USP8+/- and USP8-/-) showed significantly increased pituitary ACTH expression compared to wild-type mice (p < 0.05).
- USP8-/- mice exhibited higher blood glucose and heart rates than wild-type and USP8+/- mice.
- No significant pathological changes were observed in pituitary and adrenal tissues across the groups.
Conclusions:
- USP8 knockout mice demonstrate potential as a valuable animal model for studying ACTH adenoma.
- These findings highlight the critical role of USP8 in the pathogenesis of ACTH-secreting pituitary tumors.
More Related Videos
07:44Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice
Published on: February 17, 2023
03:41High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model
Published on: October 11, 2022