HEXA

Abstract: We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.

Abstract: The hydrolysis of aluminium salt solutions has been studied using 27AI and 1H n.m.r. and this has led to reliable values for the concentrations of the species of AI(H2O)63+, AI2(OH)2(H2O)84+, and AI13O4(OH)24(H2O)127+ at different degrees of hydrolysis. These ions do not account for all the aluminium in solution and another species, probably Al8(OH)20(H2O)x4+ is thought to be present. It is shown that previous controversy over the constitution of these solutions arose because of the different methods used for preparing the solutions: only the first two species exist when hydrated aluminium(III) chloride is dissolved in water whereas the highly polymeric species appear only after considerable hydrolysis has occurred at higher pH. The cations, particularly the dimer, may also be more hydrolysed than the above formulae indicate and this has probably confused the previous interpretation of the potentiometric results.