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Chuột BALB/c có tính nhạy cảm di truyền với viêm khớp và viêm cột sống do proteoglycan cho thấy sự khác biệt phụ thuộc vào колони trong độ thâm nhập của bệnh
Tóm tắt
Phức hợp tương hợp chính di truyền (H-2d) và nền tảng di truyền không phải phức hợp tương hợp chính khiến dòng chuột BALB/c rất dễ bị viêm khớp mạn tính và viêm cột sống. Mặc dù các колoni BALB/c khác nhau phát triển viêm khớp do proteoglycan và viêm cột sống do proteoglycan khi được tiêm chủng với proteoglycan sụn người, họ lại thể hiện sự khác biệt đáng kể về sự thâm nhập của bệnh mặc dù được bảo trì bởi cùng một nhà cung cấp tại cùng một hoặc một địa điểm khác. Chuột cái BALB/c (24 đến 26 tuần tuổi sau 4 tuần thích nghi) đã được tiêm một liều proteoglycan sụn dưới mức tối ưu để khám phá ngay cả những sự khác biệt nhỏ giữa 11 tiểu колoni được mua từ năm nhà cung cấp khác nhau. Các đáp ứng tế bào T đo được trong ống nghiệm, cytokines huyết thanh và (tự)kháng thể được liên hệ với điểm số biểu hiện của viêm khớp (và viêm cột sống). Các vi mạch cDNA cũng đã được thực hiện sử dụng tế bào lách của chuột BALB/cJ và BALB/cByJ (cả hai колoni từ The Jackson Laboratory, Bar Harbor, ME, USA), đại diện cho hai tiểu dòng BALB/c chính. 11 колoni BALB/c có thể được phân loại thành các nhóm đáp ứng cao (n = 3), trung bình (n = 6) và thấp (n = 2) dựa trên điểm số viêm khớp của chúng. Trong khi các kiểu hình lâm sàng cho thấy sự khác biệt đáng kể, chỉ có một vài tham số miễn dịch tương quan với các bất thường lâm sàng hoặc mô bệnh học, và dường như không có tham số nào trong số đó ảnh hưởng đến những khác biệt trong các kiểu hình lâm sàng đã được thay đổi (thời gian khởi phát, độ nặng hoặc tỷ lệ mắc viêm khớp, hoặc độ nặng và tiến triển của viêm cột sống). Kiểm tra Affymetrix (Affymetrix, Santa Clara, CA, USA) đã khám phá 77 gen biểu hiện khác biệt (tại mức độ có ý nghĩa, P < 0.05) giữa BALB/cJ (gốc) của The Jackson Laboratory và BALB/cByJ (được chuyển từ Viện Quốc gia sức khoẻ, Bethesda, MD, USA). Mười bốn trên tổng số 77 gen biểu hiện khác biệt có chức năng chưa xác định; 24 trong số 77 gen cho thấy sự khác biệt hơn hai lần, và chỉ có 8 gen được kích thích bởi tiêm chủng, một số trong cả hai колoni. Sử dụng các tiểu колoni khác nhau của dòng BALB/c, chúng tôi có thể phát hiện sự khác biệt đáng kể trong các kiểu hình viêm khớp, biến thể đơn nucleotide (SNP), và một số lượng lớn các gen biểu hiện khác biệt, ngay cả ở các động vật không được tiêm chủng. Một số gen đã biết (và SNP) liên quan đến phản ứng miễn dịch và/hoặc viêm khớp trong dòng chuột này có tính nhạy cảm di truyền với viêm khớp, và một số gen với chức năng chưa biết có thể ảnh hưởng hoặc điều chỉnh các kiểu hình lâm sàng của viêm khớp và/hoặc viêm cột sống.
Từ khóa
#BALB/c #viêm khớp #viêm cột sống #proteoglycan #tính nhạy cảm di truyềnTài liệu tham khảo
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