Legouis R, Cohen-Salmon M, Del Castillo I, Petit C
Unité de Génétique Moléculaire Humaine, CNRS URA 1445, Institut Pasteur, Paris, France.
Biomed Pharmacother. 1994;48(5-6):241-6. doi: 10.1016/0753-3322(94)90139-2.
Kallmann de Morsier Syndrome is defined by the association of an hypogonadism with an anosmia. The hypogonadism is due to a deficiency of GnRH (gonadotropin-releasing hormone). Olfactory bulbs and tracts are underdeveloped in the patients. Embryological studies have indicated that the migration of GnRH neurons and the axonal extension of olfactory neurons, which both originate in the olfactory epithelium during embryogenesis, were impaired in a fetus affected by X-linked Kallmann Syndrome. By a positional cloning strategy, we have isolated the KAL gene, responsible for the X-linked form of the disease. The gene consists of 14 exons. A highly homologous pseudogene on the Y chromosome has been characterized. The KAL gene encodes a putative secreted protein of 680 amino acids, which contains four fibronectin type III repeats and a four disulphide core motif. The former motif is usually associated with adhesion function. The latter has been described in protein with antiprotease activity. We have isolated the chicken KAL homologue and studied its expression by in situ hybridization during late embryonic development. The gene is expressed in various neuronal populations of the central nervous system, including mitral cells of the olfactory bulbs. We suggested that the KAL protein might be involved in late neuronal differentiation.
卡尔曼 - 德莫西埃综合征的定义是性腺功能减退与嗅觉缺失同时出现。性腺功能减退是由于促性腺激素释放激素（GnRH）缺乏所致。患者的嗅球和嗅束发育不全。胚胎学研究表明，在患有X连锁卡尔曼综合征的胎儿中，起源于胚胎期嗅上皮的GnRH神经元迁移和嗅觉神经元的轴突延伸均受到损害。通过定位克隆策略，我们分离出了导致该疾病X连锁形式的KAL基因。该基因由14个外显子组成。Y染色体上有一个高度同源的假基因已被鉴定。KAL基因编码一种推定的680个氨基酸的分泌蛋白，它含有四个III型纤连蛋白重复序列和一个四二硫键核心基序。前一个基序通常与黏附功能相关。后一个基序在具有抗蛋白酶活性的蛋白质中被描述过。我们分离出了鸡的KAL同源物，并通过原位杂交研究了其在胚胎发育后期的表达。该基因在中枢神经系统的各种神经元群体中表达，包括嗅球的二尖瓣细胞。我们认为KAL蛋白可能参与神经元的后期分化。
