SIP1 expression patterns in brain investigated by generating a SIP1-EGFP reporter knock-in mouse.

A loss of function of SIP1 (Smad interacting protein 1) in the mouse as well as in human of Mowat-Wilson syndrome results in severe and multiple defects in neural tissue development, especially in the brain. However, no detailed expression analysis of SIP1 during brain development has been previously reported. In this study, we describe the generation of an EGFP knock-in reporter mouse for the Sip1 locus and our subsequent analysis of SIP1-EGFP fusion protein expression during brain development. SIP1-EGFP expression was observed in the pyramidal neurons of the hippocampus, the dentate gyrus, and the postmitotic neurons in the cerebral cortex. In layer 5 of the cerebral cortex, SIP1-EGFP expression was complementary to the Ctip2-expressing neurons, most of which are thought to be the cortico-spinal neurons. This suggested that SIP1-EGFP expressing cells might have the specific trajectory targets other than the spinal region. We further observed SIP1-EGFP expression in oligodendrocytes of the corpus callosum and fimbria, Bergmann glial cells of the cerebellum, the olfactory bulb, and in the serotonergic and dopaminergic neurons of the raphe nuclei in the brainstem. These findings may help to clarify the unknown roles of SIP1 in these cells and the pathoetiology of Mowat-Wilson syndrome.