Genetic polydactyly / arhinencephaly mouse (Pdn / Pdn) is a homologue of Greig cephalopolysyndactyly syndrome.

多指畸形小鼠（Pdn/Pdn）的纯合子表现为轴前多指畸形和arhinecephaly畸形，其负责基因被认为是13A2-3染色体上的Gli3。Greig头多指并指综合征（GCPS）表现为特殊的面部特征，包括宽鼻根和远端趾，足和手均有多指和并指。其负责基因是7p13染色体上的GLI3。从Gli3和Gli3基因的高度同源性、表型的相似性和染色体的同一性来看，Pdn/Pdn被认为是人类GCPS的小鼠同源物。我们认为Pdn/Pdn小鼠的发育机制可以推断为GCPS的发育机制。本研究主要探讨Pdn/Pdn小鼠在嗅觉神经、嗅球形成和三叉神经方面的发育机制。1)嗅神经纤维投射的DiI研究。正常小鼠胚胎在妊娠第12天，嗅神经纤维附着并侵入端脑，在妊娠第13天，端脑前部突出形成嗅球原基。而嗅觉神经纤维在Pdn/Pdn小鼠胚胎的任何发育阶段都没有附着和侵入端脑。从这一现象来看，嗅球的突出不是由于嗅神经纤维不附着于端脑而引起的。2) Pdn/Pdn胚胎嗅神经纤维未侵及中枢神经系统，在脑膜内，嗅神经纤维在前脑或大脑半球下形成缠结团块。电镜观察发现，Pdn/Pdn新生儿筛网板上嗅觉神经缠结处未见突触。3) Pdn/Pdn未形成嗅球和副嗅球。而构建嗅球的原始二尖瓣/簇状细胞在Pdn/Pdn中采用抗ocam（嗅细胞粘附分子）抗体免疫组化染色检测。这意味着端脑前部有分化为没有嗅觉神经支配的二尖瓣/簇状细胞的宿命。然后，通过嗅神经纤维的神经支配诱导嗅球从端脑突出，直至妊娠第12天。因此，我们认为嗅球的形成机制有两个步骤。4) Pdn/Pdn出生后很快死亡，不吮吸母亲的乳汁。人们认为，老鼠的新生儿会用它们的须或嗅觉来搜索母亲的乳头。须受三叉神经支配。采用抗神经丝抗体免疫组化染色法对Pdn/Pdn小鼠胚胎三叉神经纤维进行研究。Pdn/Pdn中三叉神经节、三叉神经纤维束的生长及其须囊的神经支配均正常。如上所述，Pdn/Pdn在嗅觉系统中存在异常，因此Pdn/Pdn的哺乳功能障碍被认为是嗅觉系统功能障碍引起的。少

The homozygote of Polydactyly mouse (Pdn/Pdn) shows preaxial polydactyly and arhinecephaly, and its responsible gene has been considered to be Gli3 on chromosome 13A2-3. Greig cephalopolysyndactyly syndrome (GCPS) shows peculiar facial feature including broad nasal root and telecanthus, and polydactyly arid syndactyly both In the foot and hand. Its responsible gene is GLI3 on chromosome 7p13. From the high homology between Gli3 and GLI3 genes, the similarity of phenotypes, and synteny of their chromosomes, Pdn/Pdn was considered to be a mouse homologue of human GCPS.It was thought that developmental mechanisms in Pdn/Pdn mouse can be extrapolated to the developmental mechanism of GCPS.In this study, developmental mechanisms of Pdn/Pdn mouse was investigated especially in the olfactory nerve, olfactory bulb formation and trigeminal nerve.1) Olfactory nerve fiber projection were investigated by DiI.The olfactory nerve fibers attached and invaded into the telencephalon on day 12 of gestat … More ion, and anterior part of telencephalon protruded to form the olfactory bulb primodium on day 13 of gestation in the normal mouse embryos. While, the olfactory nerve fibers did not attach and invade the telencephalon during any developmental stages in Pdn/Pdn mouse embryos. From thIs phenomenon, it was suggested that the protrusion of the olfactory bulb was not induced by the non-attachment of the olfactory nerve fibers to the telencephalon.2) Olfactory nerve fibers did not invade the central nervous systems, and olfactory nerve fibers formed a tangled mass under the forebrain or cerebral hemisphere in the meninges in Pdn/Pdn embryos. In the electron microscopic observations, there were no synaps in the tangle of the olfactory nerve on the cribriform plate in Pdn/Pdn newborns.3) Olfactory bulb and accessory olfactory bulb were not formed in Pdn/Pdn. But, primordial mitral/tufted cells which construct the olafactory bulb were detected by the immunohistochemical staining using anti-OCAM (olfactory cell adhesion molecule) antibody in Pdn/Pdn. That means, anterior part of telencephalon has a destine to differentiate to be the mitral/tufted cells without olfactory nerve innervation. Then, protrusion of the olfactory bulb from the telencephalon is induced by the innervation of the olfactory nerve fibers till day 12 of gestation. Thus, it was suggested that the mechanisms to form the olfactory bulb have 2 steps.4) Pdn/Pdn die soon after birth without sucking their mother's milk. it was considered that mouse newborns search their mother's nipples using either their whisker or olfaction. Whisker is innervated by the trigeminal nerve. Trigeminal nerve fibers in Pdn/Pdn mouse embryos were investigated by the immunohistochemical staining using anti-neurofilament antibody. Trigeminal ganglion, outgrowth of trigeminla nerve fiber bundles, and its innervation of the whisker follicles were normal in Pdn/Pdn. Pdn/Pdn has abnormalities in the olfactory system as mentioned above, so suckling dysfuction in Pdn/Pdn was considered to be caused by the dysfunction of the olfactory system. Less