Dehart D B, Lanoue L, Tint G S, Sulik K K
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599-7090, USA.
Am J Med Genet. 1997 Jan 31;68(3):328-37. doi: 10.1002/(sici)1096-8628(19970131)68:3<328::aid-ajmg15>3.0.co;2-v.
The fact that Smith-Lemli-Opitz syndrome (SLOS), a syndrome comprising major malformations involving a number of organ systems, results from an abnormality in cholesterol biosynthesis, was discovered only recently. Utilizing a drug (BM 15.766) to inhibit the same step in cholesterol biosynthesis as is abnormal in those affected with SLOS, we have developed a rat model that presents with abnormalities observed as early as gestational day 12 that appear to be consistent with some of those subsequent malformations that comprise the human syndrome. Abnormalities of the brain and face include deficiency in the midline region of the upper face, narrowing of the forebrain hemispheres and of the cerebral aqueduct, and deficiency in the developing lower jaw. Associated pathogenesis, as observed on gestational day 11 in histological sections and with scanning electron microscopy, involves abnormal cell populations at the rim of the developing forebrain and in the alar plate of the lower midbrain and hind-brain. The affected cells appear abnormally rounded up, having apparently lost their normal cell contacts. The potential basis for the selective vulnerability of this cell population and the impact of its vulnerability relative to subsequent dysmorphogenesis is discussed.
史密斯-勒米-奥皮茨综合征（SLOS）是一种涉及多个器官系统的主要畸形综合征，其由胆固醇生物合成异常引起，这一事实直到最近才被发现。利用一种药物（BM 15.766）来抑制胆固醇生物合成中与SLOS患者异常相同的步骤，我们建立了一种大鼠模型，该模型早在妊娠第12天就出现了异常，这些异常似乎与构成人类综合征的一些后续畸形一致。脑和面部的异常包括上脸中线区域缺失、前脑半球和脑导水管变窄以及发育中的下颌骨缺失。在妊娠第11天的组织学切片和扫描电子显微镜观察中发现的相关发病机制涉及发育中的前脑边缘以及中脑下部和后脑翼板中的异常细胞群。受影响的细胞看起来异常圆润，显然失去了正常的细胞接触。本文讨论了该细胞群选择性易损性的潜在基础及其易损性对后续畸形发生的影响。
