Godfrey V L, Wilkinson J E, Russell L B
Biology Division, Oak Ridge National Laboratory, TN 37831-8077.
Am J Pathol. 1991 Jun;138(6):1379-87.
Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising scurfy mice in a specific-pathogen-free environment does not alter disease expression. Thus, while our findings indicate that scurfy disease may be the result of immune dysfunction, it is not a classic immunodeficiency.
“鳞屑”（sf）是一种自发的、X连锁隐性突变，定位于X染色体的最近端，距“稀毛”（spf）约2厘摩。sf半合子表现出多种临床病症，在14日龄时明显，包括眼睑、耳朵和尾巴的鳞屑和结痂、发育迟缓、生殖乳头发红肿胀、贫血、恶病质及早期死亡（平均24天）。我们的研究表明，半合子“鳞屑”的表型并非如所认为的那样是人类X连锁鱼鳞病的模型，而是一种主要影响淋巴网状系统以及可能影响造血系统的疾病。大体病变包括明显的脾肿大、肝肿大、淋巴结肿大以及耳朵不同程度的增厚。特征性组织学病变是外周淋巴结、脾脏、肝脏和皮肤的淋巴细胞组织细胞增生和浸润。在常规苏木精和伊红染色切片中，这些病变破坏淋巴结结构、增厚真皮并在肝脏形成结节状门脉浸润。“鳞屑”病变特征性地包含一群大的母细胞样细胞，其核圆形至椭圆形，染色质呈泡状，有明显的单个核仁。有时在肾脏、心脏、胰腺、肺和肠系膜中发现淋巴细胞、巨噬细胞和粒细胞的混合血管周围浸润。肝脏和脾脏有过度造血现象。表达B220或Thy - 1抗原的细胞定位于淋巴结和脾脏的适当区域，但在门脉浸润中很少见，在皮肤中不存在。血清IgG有明显的多克隆增加、严重的库姆斯阳性贫血以及伴有非典型单核细胞的白细胞增多。“鳞屑”小鼠抗核抗体呈阴性。尽管其淋巴网状系统形态异常，但“鳞屑”小鼠能在常规环境中生存，无机会性感染迹象。在无特定病原体环境中饲养“鳞屑”小鼠并不会改变疾病表现。因此，虽然我们的研究结果表明“鳞屑”病可能是免疫功能障碍的结果，但它并非典型的免疫缺陷病。
