De Lisle R C
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160, USA.
Am J Physiol. 1995 Apr;268(4 Pt 1):G717-23. doi: 10.1152/ajpgi.1995.268.4.G717.
The CFTR (-/-) mouse model of cystic fibrosis (CF) has revealed that the mouse pancreatic duct has a Ca(2+)-regulated chloride conductance that allows ductal electrolyte transport to remain unaffected by loss of the cystic fibrosis transmembrane conductance regulator (CFTR). Therefore, this model provides a unique opportunity to investigate effects of CF on the acinar tissue. It has been reported that exocrine secretions contain higher levels of sulfate in CF. We discovered in CFTR(-/-) acini that gp300, the major sulfated glycoprotein of the mouse acinar cell, has increased steady-state and biosynthetic levels. However, there are no apparent changes in sulfate or carbohydrate composition of gp300, indicating that posttranslational processing of this sulfated glycoprotein is not altered in CF. In addition to the increase in gp300, the morphology of CF acinar tissue is dramatically altered: acinar lumina of CFTR(-/-) mice are greatly dilated and filled with aggregated protein. gp300, which in the normal tissue is mainly localized to the zymogen granule membrane, was found to line the distended luminal membranes in the CF tissue. These results demonstrate that the acinar tissue is affected in the CF mouse and that expression of the major sulfated glycoprotein is also increased. It is suggested that increased expression of gp300 in CFTR(-/-) mice may cause poorly soluble exocrine protein secretion, contributing to the development of CF in the pancreas.
囊性纤维化（CF）的CFTR（-/-）小鼠模型显示，小鼠胰管具有Ca（2+）调节的氯电导，使导管电解质转运不受囊性纤维化跨膜电导调节因子（CFTR）缺失的影响。因此，该模型为研究CF对腺泡组织的影响提供了独特的机会。据报道，CF患者的外分泌分泌物中硫酸盐含量较高。我们在CFTR（-/-）腺泡中发现，小鼠腺泡细胞的主要硫酸化糖蛋白gp300的稳态水平和生物合成水平有所增加。然而，gp300的硫酸盐或碳水化合物组成没有明显变化，这表明这种硫酸化糖蛋白的翻译后加工在CF中没有改变。除了gp300增加外，CF腺泡组织的形态也发生了显著改变：CFTR（-/-）小鼠的腺泡腔大大扩张，充满了聚集的蛋白质。在正常组织中主要定位于酶原颗粒膜的gp300，在CF组织中被发现排列在扩张的腔膜上。这些结果表明，CF小鼠的腺泡组织受到影响，主要硫酸化糖蛋白的表达也增加。有人提出，CFTR（-/-）小鼠中gp300表达的增加可能导致难溶性外分泌蛋白分泌，从而促进胰腺CF的发展。
