Peters L L, Jindel H K, Gwynn B, Korsgren C, John K M, Lux S E, Mohandas N, Cohen C M, Cho M R, Golan D E, Brugnara C
The Jackson Laboratory, Bar Harbor, Maine 04609, USA Department of Biomedical Research, St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
J Clin Invest. 1999 Jun;103(11):1527-37. doi: 10.1172/JCI5766.
Protein 4.2 is a major component of the red blood cell (RBC) membrane skeleton. We used targeted mutagenesis in embryonic stem (ES) cells to elucidate protein 4.2 functions in vivo. Protein 4. 2-null (4.2(-/-)) mice have mild hereditary spherocytosis (HS). Scanning electron microscopy and ektacytometry confirm loss of membrane surface in 4.2(-/-) RBCs. The membrane skeleton architecture is intact, and the spectrin and ankyrin content of 4. 2(-/-) RBCs are normal. Band 3 and band 3-mediated anion transport are decreased. Protein 4.2(-/-) RBCs show altered cation content (increased K+/decreased Na+)resulting in dehydration. The passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl cotransporters, the Na/H exchanger, and the Gardos channel in 4. 2(-/-) RBCs are significantly increased. Protein 4.2(-/-) RBCs demonstrate an abnormal regulation of cation transport by cell volume. Cell shrinkage induces a greater activation of Na/H exchange and Na-K-2Cl cotransport in 4.2(-/-) RBCs compared with controls. The increased passive Na+ permeability of 4.2(-/-) RBCs is also dependent on cell shrinkage. We conclude that protein 4.2 is important in the maintenance of normal surface area in RBCs and for normal RBC cation transport.
蛋白4.2是红细胞（RBC）膜骨架的主要成分。我们利用胚胎干细胞（ES）中的靶向诱变来阐明蛋白4.2在体内的功能。蛋白4.2基因敲除（4.2(-/-)）小鼠患有轻度遗传性球形红细胞增多症（HS）。扫描电子显微镜和红细胞变形性测定证实4.2(-/-)红细胞的膜表面积减少。膜骨架结构完整，4.2(-/-)红细胞的血影蛋白和锚蛋白含量正常。带3及带3介导的阴离子转运减少。蛋白4.2(-/-)红细胞显示阳离子含量改变（钾离子增加/钠离子减少），导致脱水。4.2(-/-)红细胞的被动钠离子通透性以及钠-钾-2氯共转运体、钾-氯共转运体、钠/氢交换体和加尔多斯通道的活性显著增加。蛋白4.2(-/-)红细胞表现出细胞体积对阳离子转运的异常调节。与对照组相比，细胞收缩在4.2(-/-)红细胞中诱导钠/氢交换和钠-钾-2氯共转运的更大激活。4.2(-/-)红细胞被动钠离子通透性的增加也依赖于细胞收缩。我们得出结论，蛋白4.2对于维持红细胞的正常表面积和正常的红细胞阳离子转运很重要。
