Pathology of G_M2 Gangliosidosis in Jacob Sheep

Abstract

The G M2 gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G M2 activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G M2 gangliosidosis. This form of G M2 gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.

Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

“…10 The inflammatory response may precede the clinical manifestations, 11 and further perpetuate neurological injury. 12 GM2 gangliosidoses occur naturally in several species, 13,14 but the mouse is more amenable for testing new therapies. Two Sandhoff mouse models have been generated by targeted disruption of the Hexb gene.…”

Occipital condylar dysplasia in a Jacob lamb (<i>Ovis aries</i>)

“…A further clinical differential was the lysosomal storage disease, GM2 gangliosidosis. This has recently been described in Jacob sheep in the UK and USA (Torres et al, 2010;Porter et al, 2011;Wessels et al, 2014). GM2 gangliosidosis manifests as progressive ataxia in six-to-eight month-old lambs, and progresses over a period of ten days to eight weeks.…”

Study of Genetics Mutations in HEXA Gene for Induced Tay-Sachs Disease in Human, Tabriz, Iran

“…Ethanol and the sediment was removed and placed at room temperature until completely dry deposition. The precipitate was dissolved in 20μl sterile water and at a later stage, the concentration of extracted RNA was determined [26][27][28][29][30].…”