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Feasibility analysis of ACTH adenoma model in USP8–/– mice
Affiliations- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
open access
Abstract
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.
Abstract
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.
Keywords
USP8; Cushing’s disease; animal model; ACTH adenoma
About this articleTitle
Feasibility analysis of ACTH adenoma model in USP8–/– mice
Journal
Issue
Article type
Original paper
Pages
181-189
Published online
2023-03-10
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2223
Article views/downloads
417
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2023;74(2):181-189.
Keywords
USP8
Cushing’s disease
animal model
ACTH adenoma
Authors
Jia Li
Na Wu
Dimin Zhu
Yonghong Zhu
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