Boivin G P, Schultheis P J, Shull G E, Stemmermann G N
Department of Pathology and Laboratory Medicine, University of Cincinnati School of Medicine, Ohio 45267-0529, USA.
Comp Med. 2000 Oct;50(5):511-5.
Mice lacking the NHE2 Na+/H+ gene develop gastritis of the glandular mucosa as early as the tenth day of life, achieving maximal intensity of inflammation from 17 to 19 days after birth and maximal atrophy at one year. We assessed the effects of this process in such mice to 16 months of age. The stomach of NHE2 null mutants was examined at 10, 17 to 20, 24 to 35 and 49 to 70 days, and at 12 to 16 months. The NHE2 wild-type (+/+) and NHE2 heterozygous (+/-) mice were compared with the NHE2 homozygous mutant mice (-/-). The stomach of the mutant mice at all ages was characterized by a substantially reduced number of parietal cells. The 10-day-old mouse stomach had a transmural infiltrate of primarily neutrophils. With increasing age, neutrophils were replaced by lymphocytes and plasma cells in the glandular mucosa of the mutant mice. Young adult 49- to 70-day-old mice had surface cell hyperplasia and expansion of the replicating cell population. Hyperplasia of enterochromaffin-like cells and antral gastrin cells accompanied profound fundic gland and surface cell hyperplasia, and became progressively more severe with increasing age of the NHE2-/- mice. Neoplasms were not found in the mutant or control mice. This gastritis differs from that of autoimmune gastritis in that it is transmural, begins in infancy, and is associated with a predominantly neutrophilic infiltrate in its early stages. Some of the histologic changes in the adult mice can be explained on the basis of prolonged achlorhydria. This mouse may be a suitable model for prolonged effects of achlorhydria.
缺乏NHE2钠/氢基因的小鼠早在出生后第十天就会出现腺性胃粘膜炎，在出生后17至19天炎症强度达到最大，一岁时萎缩最为严重。我们评估了这一过程对这类小鼠至16个月龄时的影响。在10天、17至20天、24至35天、49至70天以及12至16个月时检查NHE2基因敲除突变小鼠的胃。将NHE2野生型（+/+）和NHE2杂合型（+/-）小鼠与NHE2纯合突变小鼠（-/-）进行比较。所有年龄段突变小鼠的胃都表现为壁细胞数量大幅减少。10日龄小鼠的胃有主要为中性粒细胞的透壁浸润。随着年龄增长，突变小鼠腺性胃粘膜中的中性粒细胞被淋巴细胞和浆细胞取代。49至70日龄的年轻成年小鼠出现表面细胞增生和复制细胞群体扩大。肠嗜铬样细胞和胃窦胃泌素细胞增生伴随胃底腺和表面细胞显著增生，并且随着NHE2 -/-小鼠年龄增长逐渐变得更加严重。在突变小鼠或对照小鼠中均未发现肿瘤。这种胃炎与自身免疫性胃炎不同，它是透壁性的，始于婴儿期，并且在早期主要与嗜中性粒细胞浸润相关。成年小鼠的一些组织学变化可以基于长期胃酸缺乏来解释。这种小鼠可能是胃酸缺乏长期影响的合适模型。
