Mouse Chromosome 13

Chair of Committee for Mouse Chromosome 13     

Solvation properties of ubiquinone-10 in solvents of different polarity

The solvation properties of ubiquinone-10 and ubiquinol-10 in a wide variety of solvents of polarity varying from alkanes to water are reported. Greatest solubility is observed in solvents of intermediate polarity and particularly where low polarity is combined with a pronounced tendency to interact with the benzoquinone substituent of the ubiquinone molecule. This includes solvents like chloroform and benzene. Ubiquinone-10 is somewhat less polar than ubiquinol-10 as judged by comparative solubilities of the two molecules. Proton-NMR chemical shift measurements and aggregation studies in selected solvents indicate that in ubiquinone-10 in the liquid phase and in solution in hydrocarbons like dodecane the molecules have a preferred association possibly involving stacking of the benzoquinone rings. Surface balance studies indicated that the surface-active character of ubiquinone-10 is relatively weak and only in a comparatively polar and highly structured solvent, formamide, was there evidence of an effect on surface tension of the solvent. The critical micelle concentratiom in this solvent was estimated to be about 5 M on the basis of surface tension measurements. Ubiquinone-10 is well known to form virtually insoluble monolayers at the air/water interface. Studies of the partition of ubiquinone-10 in binary mixtures of solvents suggest that the interaction of the benzoquinone ring substituent with structured polar solvents is considerably weaker than the internal cohesion between molecules of the solvent. No evidence on the basis of wide-angle X-ray diffraction measurements was obtained to indicate that solvent molecules were a component of the crystal lattice of ubiquinone-10 that had precipitated from solvent mixtures.     

Expression by human fetal organs of organ-specific cancer neoantigens as measured by leukocyte adherence inhibition

Summary Human cancers express organ-specific cancer neoantigens (OSN) as determined by in vitro leukocyte responses to extracts of cancers by the tumor host. In this study, we determined whether the OSNs were normal developmental proteins that were expressed by fetal organs and re-expressed with oncogenesis. Fetal extracts, principally of lung and colon but also of liver and kidney, were tested for their ability to induce leukocyte adherence inhibition (LAI) as compared to extracts from adult tissues of the same organ. Leukocytes from lung cancer patients showed positive LAI responses to 13- and 19-week fetal lung tissue. Likewise, leukocytes from colon cancer patients showed positive LAI responses to 14- and 19-week fetal colon tissue, whereas leukocytes from control subjects did not. Neither group responded positively to 21-week fetal organs. Criss-cross experiments showed that the fetal antigen was organ specific. Multiparous pregnant women showed positive LAI responses to cancer extracts but not to extracts from normal tissues of the same organ. The pattern of the LAI response was bell-shaped. Positive LAI responses to lung and breast cancer were detected at 4 to 7 months gestation and peaked at 5 months. To the fetal colon, LAI positive responses were detected at 5 to 8 months gestation, with the peak response at 6 months. The results indicate that OSN of cancers are also expressed by fetal organs and sufficient antigen is shed by fetal organs to sensitize pregnant women. Older fetal organs (21 weeks) and adult organs do not express an immunogenic or antigenic OSN.Supported by a grant from the National Cancer Institute of Canada     

Clinical and biochemical studies in three patients with severe early infantile Cockayne syndrome

Summary We present clinical and biochemical data from three patients with severe Cockayne syndrome (CS) of very early onset. Unlike in classic CS, signs became evident in the first weeks of life and led to unusually early death. Fibroblasts from two of the patients showed a complete defect of the repair of UV-induced thymine dimer lesions. They were unable to remove thymine dimer lesions from their DNA, had a severe reduction of the RNA synthesis rates after UV irradiation, and showed no reactivation of an UV-inactivated indicator gene and no DNA recondensation after UV irradiation. DNA repair investigated in these two fibroblast cell strains resembled that of xeroderma pigmentosum cells of complementation group A. In contrast, fibroblasts from the third patient showed the same in vitro repair characteristics as classic CS cells.     

Properties of Chicken Lens MIP Channels Reconstituted into Planar Lipid Bilayers

Membrane fractions highly enriched in chicken lens MIP (MIP28) were found to form ion channels when incorporated into planar lipid bilayers. The channels displayed prominent unitary conductances of about 60 and 290 pS in symmetric 150 mm KCl solution and were slightly anion selective. For both depolarizing and hyperpolarizing voltages, voltage sensitivity of the MIP28-induced conductance could be fit by a Boltzmann relation, symmetric around zero mV, with V ₀ = 18.5 mV, n= 4.5 and g _min/g _max= 0.17. Channel properties were not appreciably altered by pH in the range of 5.8 to 7, although channel incorporation was observed to occur more frequently at lower pH values. Calcium, at millimolar concentrations, decreased the channel mean open time. Partial proteolysis of MIP28 to yield MIP21 did not appreciably affect single-channel conductance or voltage sensitivity of the reconstituted channels. MIP28 was not phosphorylated by cAMP dependent protein kinase (PKA). Although unitary conductance and selectivity of the chicken MIP channel are similar to those reported for the bovine MIP (MIP26), the voltage sensitivity of MIP28 was higher than that of the bovine homologue, and voltage sensitivity of MIP28 was not modulated by treatments previously shown to affect MIP26 voltage gating (partial proteolysis and protein phosphorylation by PKA: (Ehring et al., 1990). The existence of such strikingly different functional properties in highly homologous channel isoforms may provide a useful system for exploration of the structure-function relations of MIP channels. Received: 27 March 1996/Revised: 5 August 1996