MICE LACKING SYNAPTOPHYSIN REPRODUCE AND FORM TYPICAL SYNAPTIC VESICLES

Synaptophysin is one of the major integral membrane proteins of the sm all (30-50 nm diameter) electron-translucent transmitter-containing ve sicles in neurons and of similar vesicles in neuroendocrine cells. Sin ce its expression is tightly linked to the occurrence of these vesicle types, we mutated the X-chromosomally located synaptophysin gene in e mbryonic stem cells for the generation of synaptophysin-deficient mice in order to study the consequence of synaptophysin ablation for the f ormation and function of such vesicles in vivo. The behavior and appea rance of mice lacking synaptophysin was indistinguishable from that of their litter mates and reproductive capacity was comparable to normal mice. Furthermore, no drastic compensatory changes were noted in the expression of several other neuronal polypeptides or in the mRNA level s of synaptophysin isoforms, the closely related neuronal synaptoporin /synaptophysinII, and the ubiquitous pantophysin. Immunofluorescence m icroscopy of several neuronal and neuroendocrine tissues showed that o verall tissue architecture was maintained in the absence of synaptophy sin, and that the distribution of other synaptic vesicle components wa s not visibly affected. In electron-microscopic preparations, large nu mbers of vesicles with a diameter of 39.9 nm and an electron-transluce nt interior were seen in synaptic regions of synaptophysin-deficient m ice; these vesicles could be labeled by antibodies against synaptic ve sicle proteins, such as synaptobrevin 2.