Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum

The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.     

In vitro dedifferentiation of fetal porcine pancreatic tissue prior to transplantation as islet-like cell clusters

The fetal porcine pancreas under experimental conditions can be transplanted in the form of explants or islet-like cell clusters (ICCs) to normalize blood glucose levels in diabetic recipients. ICCs are released from the collagenase-digested pancreas and require a 4- to 5-day culture period for their complete formation. In order to maximize insulin producing beta cell differentiation following transplantation, an understanding of ICC development is essential to utilize this alternative treatment for type 1 diabetes. In this study a role is proposed for exocrine cells in the generation of the multipotent pancreatic precursor cells during the culture period. Acinar cells undergo dedifferentiation during the initial stages of the culture period into multipotent pancreatic precursor cells, previously called protodifferentiated cells. The progressive loss of exocrine differentiation appears to involve rapid degranulation of zymogen granules by exocytosis and loss of the prominent secretory apparatus. These processes occur in parallel with a significant reduction in the expression of lipase in the period from day 0 to day 5 and simultaneously there is an increase in the epithelioid/ductal cell marker, cytokeratin 20. Using proliferating cell nuclear antigen, cell proliferation during the culture period does not appear to account for the increase in epithelioid/ductal cells. Further the rates of apoptosis and necrosis which were identified using the TUNEL technique and propidium iodide, respectively, do not appear to account for the reduction in exocrine cell numbers. Exocrine cell dedifferentiation appears to increase the pool of protodifferentiated cells which have the potential to develop into the insulin-producing beta-cell population following transplantation into the diabetic recipient