Mutant vasopressin precursor producing cells of the homozygous Brattleboro rat as a model for co-expression of neuropeptides.

The homozygous Brattleboro rat (di/di) synthesizes a VP precursor with an abnormal C terminus, which is not transported from the rough endoplasmic reticulum to the Golgi apparatus. In addition, the phenotypic expression of co-existing peptides is differentially disturbed. Ang II and 7B2 are two of the peptides which are not detectable, whereas other peptides (e.g. galanin) are clearly expressed in mutant VP cells. During postnatal life a small but increasing number of solitary post-mitotic VP neurons of the di/di rat undergoes a switch to a heterozygous phenotype. At the same time Ang II and 7B2 show up again in these heterozygous cells, which suggests that for the expression of 7B2, but not for that of other peptides (e.g. galanin), a normal VP precursor is required. A possible underlying mechanism (i.e. the existence of several domains on the endoplasmic reticulum involved in the translocation of sets of neuropeptides) for this differential phenotypic expression of co-existing peptides is discussed.