Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse
Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse
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DOI：
10.1038/ng1418
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发表时间：
2004-09-01
期刊：
影响因子：
30.8
通讯作者：
Katsanis, N
中科院分区：
文献类型：
--
作者：
Kulaga, HM;Leitch, CC;Katsanis, N
纤毛缺陷与几种人类疾病有关，包括Kartagener综合征(1)、多囊肾病（2,3）、肾性肾病(4)和脑积水(5)。我们提出Bardet-Biedl综合征（BBS）的多性表型，包括视网膜变性、躯干肥胖、肾脏和肢体畸形以及发育迟缓，是由基底体和纤毛功能障碍引起的（6,7）。在这里，我们显示患有BBS的个体有部分或完全的嗅觉缺失。为了测试这种表型是否由嗅觉感觉神经元的纤毛缺陷引起，我们检测了Bbs1或Bbs4缺失的小鼠。两种BBS蛋白的功能丧失都会影响嗅觉上皮，但不会影响呼吸上皮，导致纤毛边缘严重减少，树突微管网络紊乱，嗅觉纤毛蛋白被困在树突和细胞体中。我们的数据表明，BBS蛋白在哺乳动物纤毛细胞的微管组织中起作用，嗅觉缺失可能是其他疑似纤毛受损伤的多效性疾病的有用决定因素。
Defects in cilia are associated with several human disorders, including Kartagener syndrome(1), polycystic kidney disease(2,3), nephronophthisis(4) and hydrocephalus(5). We proposed that the pleiotropic phenotype of Bardet-Biedl syndrome (BBS), which encompasses retinal degeneration, truncal obesity, renal and limb malformations and developmental delay, is due to dysfunction of basal bodies and cilia(6,7). Here we show that individuals with BBS have partial or complete anosmia. To test whether this phenotype is caused by ciliary defects of olfactory sensory neurons, we examined mice with deletions of Bbs1 or Bbs4. Loss of function of either BBS protein affected the olfactory, but not the respiratory, epithelium, causing severe reduction of the ciliated border, disorganization of the dendritic microtubule network and trapping of olfactory ciliary proteins in dendrites and cell bodies. Our data indicate that BBS proteins have a role in the microtubule organization of mammalian ciliated cells and that anosmia might be a useful determinant of other pleiotropic disorders with a suspected ciliary involvement.