Low levels of mouse sperm chromatin fragmentation delay embryo development.

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner.

Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre.

Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound and synchronous demyelination of the corpus callosum, which was virtually complete by 4 weeks of exposure. Interestingly, even in the face of a continued exposure to cuprizone, there was spontaneous remyelination 2 weeks later. This remyelination preferentially involved smaller calibre axons.

Distribution of enzyme-bearing cells in GM2 gangliosidosis mice: regionally specific pattern of cellular infiltration following bone marrow transplantation.

Tissue distribution of beta-hexosaminidase was investigated using 5-bromo-4-chloro-3-indolyl N-acetyl beta-D-glucosaminide (X-Hex) as substrate in wild-type mice, four GM2 gangliosidosis model mice (Hexa-/-, Hexb-/-, Gm2a-/- and Hexa-/-Hexb-/-) and Hexb-/- mice that received bone marrow transplantation (BMT). In wild-type mice histochemical localization of beta-hexosaminidase was detected in the perikarya of the majority of neurons, small process-bearing microglial cells, perivascular macrophages, and macrophages in the choroid plexus and leptomeninges. X-Hex positivity was also noted in the renal tubular epithelium and macrophages in the liver and spleen.

Mice deficient in all forms of lysosomal beta-hexosaminidase show mucopolysaccharidosis-like pathology.

Lysosomal beta-hexosaminidase consists of 2 subunits, alpha and beta. Mutations in the alpha-subunit gene cause Tay-Sachs disease, while mutations in the beta-subunit gene cause Sandhoff disease. Mice generated by targeted disruption of either the alpha- or beta-subunit genes displayed the pathological features of Tay-Sachs disease or Sandhoff disease, respectively.

Neuropathology of mice with targeted disruption of Hexa gene, a model of Tay-Sachs disease.

A murine model of Tay-Sachs disease, the prototype of the GM2 gangliosidoses, was produced through the targeted disruption of the Hexa gene encoding the subunit of alpha-hexosaminidase A. The mice were completely devoid of beta-hexosaminidase A activity and accumulated GM2 ganglioside in the CNS in an age-dependent manner. Neurons with membranous cytoplasmic bodies (MCBs), identical to those described in Tay-Sachs disease, were identified in the brain of these mice.