Dottori M, Hartley L, Galea M, Paxinos G, Polizzotto M, Kilpatrick T, Bartlett P F, Murphy M, Köntgen F, Boyd A W
Queensland Institute for Medical Research, Royal Brisbane Hospital, Herston, Queensland 4029, Australia.
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13248-53. doi: 10.1073/pnas.95.22.13248.
Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.
酪氨酸激酶受体Eph家族的成员已被证明参与发育过程的调控，尤其是在发育中的神经系统中对轴突导向的调控。通过构建EphA4（Sek1）受体的无效突变小鼠来探究其功能。EphA4基因发生无效突变的小鼠能够存活且可育，但存在严重的运动功能障碍，表现为肢体运动协调性丧失，进而出现类似袋鼠跳跃的步态。与观察到的表型一致，解剖学研究和顺行示踪实验表明，无效突变动物的延髓和脊髓内的皮质脊髓束存在重大破坏。这些结果证明了EphA4在建立皮质脊髓投射中起关键作用。
