Connexin-36 (Cx36) is the only gap junction protein that has been unambiguously identified in rodent pancreatic beta-cells. However, properties of gap junction channel unitary currents between beta-cells remain unrevealed. To address whether Cx36 forms functional channels in beta-cells, we characterized biophysical properties of macro- and microscopic junctional currents recorded from dual whole cell voltage clamp isolated pairs of dispersed mouse beta-cells. Electrical coupling was recorded in 80% of cell pairs with a junctional conductance (g(j)) of 355 +/- 45 pS (n = 20). Transjunctional voltage dependence was identified in three of seven cell pairs with high-input membrane resistances. Normalized steady-state g(j) (Gj) and transjunctional-voltage relation were well described by a two-state Boltzmann equation [maximal conductance (Gmax) = 1.0, voltage-insensitive conductance (Gmin) = 0.3 and 0.28, voltage gating sensitivity (A) = 0.21 and 0.23, and voltage at which one-half of the initial voltage-dependent conductance was reached (Vo) = -85 and 87 mV for negative and positive potentials, respectively]. Halothane reversibly uncoupled beta-cell pairs, and, during recovery, unitary conductances of 5-10 pS were recorded while using patch pipettes containing mainly CsCl. Although these properties are similar to those previously described for Cx36 channels in mammalian cell systems, we found that beta-cell junctional currents were insensitive to quinine. Cx36 transcript and protein expression in islets and freshly dispersed cell preparations was confirmed by RT-PCR and immunofluorescence. In conclusion, biophysical properties of junctional channels between beta-cells are similar but not identical to those previously described for homomeric Cx36 channels. Cell type-specific mechanisms that may account for these differences are discussed.

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We describe clinical, cytogenetic, endocrine, and histopathological findings in 16 patients with mixed gonadal dysgenesis (MGD). All patients except 1 presented genital ambiguity and 10 of them had Ullrich-Turner manifestations. The 45,X/46,XY karyotype was the most frequent with a predominance of 45,X cells in both peripheral lymphocytes and gonads. In all cases Müllerian and Wolffian remnants and/or derivatives were found and in some patients both Wolffian- and Müllerian-derived structures were identified on the streak or testicular side. Postpubertal patients exhibited variable degrees of virilization and all of them had hypergonadotropism coexisting with low to normal baseline serum levels of testosterone; their testicular response to human chorionic gonadotropin (HCG) in terms of testosterone secretion was also variable, ranging from minimal to almost a normal response. All prepubertal patients but 1 had normal baseline levels of pituitary gonadotropins and testosterone and their gonadal response to the HCG challenge was highly variable. With the exception of 1 case, who had a 45,X/46,XY(p-) karyotype, no correlation between the cytogenetic data and degree of external genital ambiguity and the hormonal findings was observed. Additional information on the specific structural abnormalities involving the testis-determining gene of the Y chromosome in patients with MGD is needed in order to further understand the mechanisms responsible for the wide variability characteristic of this disorder.

The presence of the same mutation in 4 patients from 3 families indicates the increased prevalence of this mutation in a particular ethnic group, suggesting a common ancestry for the gene defect in these patients. The existence of hot spots is supported by the mutations in codons 34 and 207 which have also been found in other ethnic groups. Interestingly, the patient who presented 2 different mutations, one of them previously undescribed, was reared as a male and exhibited a more masculine phenotype. Further studies in patients with this and other mutations will be needed to verify genotype-phenotype correlation.

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