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Mô hình cá zeber góp phần vào việc nghiên cứu hội chứng nhạy cảm với hormone tăng trưởng kèm theo rối loạn miễn dịch 1 (GHISID1)
Tóm tắt
Các protein truyền tín hiệu và kích hoạt phiên mã (STAT) hoạt động ở hạ lưu của các thụ thể cytokine nhằm tạo thuận lợi cho những thay đổi về biểu hiện gen ảnh hưởng đến nhiều quá trình phát triển và duy trì cân bằng nội mô. Những bệnh nhân mang đột biến mất chức năng (LOF) trong gen STAT5B thể hiện sự chậm phát triển sau sinh do thiếu phản ứng với hormone tăng trưởng cũng như rối loạn hệ miễn dịch, một rối loạn được gọi là hội chứng nhạy cảm với hormone tăng trưởng và rối loạn miễn dịch 1 (GHISID1). Nghiên cứu này nhằm xây dựng mô hình cá zeber cho căn bệnh này bằng cách nhắm mục tiêu vào gen stat5.1 thông qua công nghệ CRISPR/Cas9 và phân tích tác động đến sự phát triển và hệ miễn dịch. Các đột biến Stat5.1 ở cá zeber có kích thước nhỏ hơn, nhưng thể hiện sự tích tụ mỡ cao hơn, đi kèm với việc điều hòa không đúng đắn các gen liên quan đến sự phát triển và chuyển hóa lipid. Những con đột biến này cũng cho thấy sự kém phát triển của quá trình tạo lympho với số lượng tế bào T giảm suốt cuộc đời, cùng với sự phá vỡ rộng rãi của khoang lympho trong giai đoạn trưởng thành, bao gồm bằng chứng về sự kích hoạt tế bào T. Tập hợp lại, những phát hiện này xác nhận rằng các đột biến Stat5.1 ở cá zeber mô phỏng các tác động lâm sàng của các đột biến LOF ở người STAT5B, thiết lập chúng thành một mô hình cho GHISID1.
Từ khóa
#STAT5B #hội chứng nhạy cảm với hormone tăng trưởng #cá zeber #đột biến LOF #hệ miễn dịchTài liệu tham khảo
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