The murine ZnT3 gene was cloned by virtue of its homology to the ZnT2 gene, which encodes a membrane protein that facilitates sequestration of zinc in endosomal vesicles. ZnT-3 protein is predicted to have six transmembrane domains and shares 52% amino acid identity with ZnT-2, with the homology extending throughout the two sequences. Human ZnT-3 cDNAs were also cloned; the amino acid sequence is 86% identical to murine ZnT-3. The mouse ZnT3 gene has 8 exons and maps to chromosome 5. Northern blot and reverse transcriptase-PCR analyses demonstrate that murine ZnT-3 expression is restricted to the brain and testis. In situ hybridization reveals that within the brain, ZnT-3 mRNA is most abundant in the hippocampus and cerebral cortex. Antibodies raised against the C-terminal tail of mouse ZnT-3 react with the projections from these neurons and produce a pattern similar to that obtained with Timm's reaction, which reveals histochemically reactive zinc within synaptic vesicles. We propose that ZnT-3 facilitates the accumulation of zinc in synaptic vesicles.

Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP; amylin). We Amyloid deposits are found in the pancreatic islets of most individuals with non-insulin-dependent diabetes mellitus (NIDDM) (1-3). The major component of islet amyloid is a 37-amino acid peptide, islet amyloid polypeptide (IAPP; amylin) (4-6), which is a normal secretory product of the pancreatic f3 cell (7,8). Formation of islet amyloid deposits from IAPP may contribute to the progressive deterioration of ,3-cell function observed in this disease (9), since IAPP-derived amyloid has been shown to be toxic to islet cells in vitro (10) and the degree of amyloid deposition is associated with the severity of hyperglycemia in monkeys (11). The mechanism leading to IAPP deposition as islet amyloid is unknown. The sequence of human IAPP (hIAPP) contains an amyloidogenic region (amino acids 20-29) that is thought to be essential for fibril formation (12, 13); however, this sequence does not appear to be the sole prerequisite since nondiabetic individuals do not usually develop islet amyloid (1-3). Thus, some additional unrecognized factor(s) must be present in NIDDM that potentiates islet amyloid formation.IAPP-derived islet amyloid has never been observed in rodents, presumably because rodent IAPP, unlike hIAPP, does not contain the necessary amyloidogenic sequence (13).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Fusion of the 310 bp located 5' of the rat growth hormone (GH) gene to the human GH structural gene resulted in somatotrope-specific expression in transgenic mice. Human GH transcripts were detected only in pituitaries of these mice, and immunocytochemical analyses revealed that this expression was limited to GH-expressing cell types. The rat GH 5' sequences were then used to direct the expression of diphtheria toxin to the GHexpressing cells of transgenic mice. A line of mice was established which lacks detectable levels of circulating GH. This deficiency resulted in dwarfism; transgenic animals grew only to half the size of nontransgenic littermates. Nearly all somatotropes were absent, as shown by GH immunostaining in the transgenic pituitaries. Prolactin (PRL)-producing lactotropes, thought to share a common cellular origin with somatotropes, were also reduced in numbers. A model for the lineal relationships between GH-and PRLsynthesizing cells is proposed.