Phillips Charlotte L, Pfeiffer Brent J, Luger Alan M, Franklin Craig L
Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
Kidney Int. 2002 Aug;62(2):383-91. doi: 10.1046/j.1523-1755.2002.00451.x.
Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proalpha2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, alpha1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, alpha1(I)2alpha2(I). Previous studies of the oim/oim mouse have focused on the musculoskeletal system, with no systematic evaluation of other organ systems.
Multiple tissues from oim/oim, oim/+ (heterozygous) and +/+ (wild-type) mice were examined for gross and histological abnormalities. Tissues were stained with (1) hematoxylin and eosin (to assess lesion formation), (2) picrosirius red (collagen content), and (3) periodic acid methenamine silver (basement membrane). Kidneys were further evaluated ultrastructurally by electron microscopy and immunohistochemically with anti-alpha1(I) and anti-alpha1(III) collagen antibodies.
Histological analyses revealed accumulations of picrosirius red-positive material, consistent with collagen, in glomeruli of 28/29 oim/oim mice, with no evidence of mesangial cell proliferation. Only the most severely affected animals had evidence of increased capillary basement membrane thickening or mild inflammation around the affected glomeruli. Electron microscopy confirmed the presence of fibrillar collagen. Immunohistochemistry with anti-alpha1(I) collagen antibodies confirmed accumulation of type I collagen in the oim/oim glomeruli. The +/+ and oim/+ kidneys had normal mesangium with no evidence of infiltration of collagenous material.
This study demonstrates the first evidence, to our knowledge, of abnormal glomerular collagen deposition associated with a type I collagen defect. Further in vivo and in vitro studies are necessary to elucidate the mechanistic, functional, and pathological significance of the oim/oim collagen glomerulopathy.
Oim/oim小鼠[成骨不全模型；原α2（I）胶原基因纯合缺失]仅合成同三聚体型I型胶原异构体α1（I）3，而无法合成正常的异三聚体型I型胶原异构体α1（I）2α2（I）。先前对Oim/oim小鼠的研究主要集中在肌肉骨骼系统，未对其他器官系统进行系统评估。
检查来自Oim/oim、Oim/+（杂合子）和+/+（野生型）小鼠的多种组织，以观察大体和组织学异常情况。组织用以下方法染色：（1）苏木精和伊红（用于评估病变形成），（2）苦味酸天狼星红（用于评估胶原含量），以及（3）高碘酸亚甲胺银（用于评估基底膜）。通过电子显微镜对肾脏进行进一步的超微结构评估，并用抗α1（I）和抗α1（III）胶原抗体进行免疫组织化学评估。
组织学分析显示，28/29只Oim/oim小鼠的肾小球中有苦味酸天狼星红阳性物质积聚，与胶原一致，且无系膜细胞增殖的证据。只有受影响最严重的动物有毛细血管基底膜增厚增加或受影响肾小球周围轻度炎症的证据。电子显微镜证实存在纤维状胶原。用抗α1（I）胶原抗体进行免疫组织化学证实Oim/oim小鼠肾小球中有I型胶原积聚。+/+和Oim/+小鼠的系膜正常，无胶原物质浸润的证据。
据我们所知，本研究首次证明了与I型胶原缺陷相关的肾小球胶原异常沉积。需要进一步的体内和体外研究来阐明Oim/oim胶原肾小球病的机制、功能和病理意义。
