The Kinesin KIF1Bbeta links neuroblastoma and neurodegenerative disease through anterograde transport of TRKA

We recently identified pathogenic KIF1Bb mutations in sympathetic nervous system malignancies that are defective in developmental apoptosis. Here we deleted KIF1Bb in the mouse sympathetic nervous system based on a cre recombination system driven by the dopamine beta hydroxylase (DBH) promoter. We observed impaired sympathetic nervous function and misexpression of genes required for sympathoadrenal lineage differentiation in KIF1Bb deficient sympathetic ganglia. We analyzed superior cervical ganglia from post-natal day 1 mice. We compared ganglia from four wild-type control animals (KIF1Bb fl/fl) with ganglia from four animals with conditional knockout of KIF1Bb (KIF1Bb fl/fl : DBHcre +/-).我们近期在存在发育性细胞凋亡缺陷的交感神经系统恶性肿瘤中，鉴定出致病性KIF1Bb突变。本研究基于多巴胺β羟化酶（dopamine beta hydroxylase, DBH）启动子驱动的Cre重组酶系统，在小鼠交感神经系统中条件性敲除KIF1Bb基因。我们观察到，KIF1Bb缺陷的交感神经节中存在交感神经功能受损，以及交感肾上腺谱系分化所需基因的异常表达。我们对出生后1天小鼠的颈上神经节进行了分析，并将4只野生型对照小鼠（基因型为KIF1Bb fl/fl）的神经节，与4只KIF1Bb条件性敲除小鼠（基因型为KIF1Bb fl/fl: DBHcre +/-）的神经节进行了对比。