Aggregation chimeras provide evidence of in vivo intercellular correction in ovine CLN6 neuronal ceroid lipofuscinosis (Batten disease).

The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are fatal, mainly childhood, inherited neurodegenerative lysosomal storage diseases. Sheep affected with a CLN6 form display progressive regionally defined glial activation and subsequent neurodegeneration, indicating that neuroinflammation may be causative of pathogenesis. In this study, aggregation chimeras were generated from homozygous unaffected normal and CLN6 affected sheep embryos, resulting in seven chimeric animals with varied proportions of normal to affected cells. These sheep were classified as affected-like, recovering-like or normal-like, based on their cell-genotype ratios and their clinical and neuropathological profiles. Neuropathological examination of the affected-like animals revealed intense glial activation, prominent storage body accumulation and severe neurodegeneration within all cortical brain regions, along with vision loss and decreasing intracranial volumes and cortical thicknesses consistent with ovine CLN6 disease. In contrast, intercellular communication affecting pathology was evident at both the gross and histological level in the normal-like and recovering-like chimeras, resulting in a lack of glial activation and rare storage body accumulation in only a few cells. Initial intracranial volumes of the recovering-like chimeras were below normal but progressively recovered to about normal by two years of age. All had normal cortical thicknesses, and none went blind. Extended neurogenesis was evident in the brains of all the chimeras. This study indicates that although CLN6 is a membrane bound protein, the consequent defect is not cell intrinsic. The lack of glial activation and inflammatory responses in the normal-like and recovering-like chimeras indicate that newly generated cells are borne into a microenvironment conducive to maturation and survival.

The immune responses of sheep after DNA immunization with, Toxoplasma gondii MAG1 antigen-with and without co-expression of ovine interleukin 6.

The aim of this study is to compare the immune responses of sheep stimulated by the intramuscular injection of a liposome formulated-DNA plasmid encoding the Toxoplasma gondii MAG1 antigen only or co-expressed with ovine IL-6. Forty-five, 2-year-old sheep were divided into four groups. Group 1 received an empty pVAXIg plasmid, group 2 no treatment, group 3 liposome formulated plasmid pVAXIgMAG1 and group 4, pVAXIgMAG1 plus pVAXovIL-6 plasmids. All the animals were inoculated at weeks 0 and 4. The injection of sheep with a plasmid encoding for MAG1 only or a MAG1 plasmid co-expressed with a plasmid encoding for ovine IL-6 produced humoral immune responses. The plasmids containing MAG1 elevated significantly serum IgG1 and IgG2 levels 2 weeks and onwards after the first injection of the plasmids. Co-expression of IL-6 with MAG1 had no effect on IG1 or IG2 levels illustrating that IL-6 in the formulation used had no modulating effect on any measured immune response.