Serial MRI Features of Canine GM1 Gangliosidosis: A Possible Imaging Biomarker for Diagnosis and Progression of the Disease

Abstract

GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies.

A Digital Atlas of the Dog Brain

“…Individual differences in brain structure as assessed by different imaging modalities, such as cortical thickness, or diffusion tensor imaging [54], may be related to normal variations of behavior or one of many disease states. Indeed, the canine is a valuable model system for many neurological diseases, including epilepsy [55]; cortical malformations such as lissencephaly [56], [57] and polymicrogyria [58], [59]; dementia [60], [61]; and focal lesions [62], [63]. Given the good registration of high-resolution anatomy with a head model, the atlas can be used to guide source localization of EEG recording in the dog [64].…”

Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency

“…The causative mutation has been identified as a deletion of the cytosine in exon 15 at nucleotide position 1647 in the putative coding region (c.1647delC) of the canine GLB1 gene [3], thereby enabling molecular diagnosis and/or genotyping with polymerase chain reaction (PCR)-based DNA tests [4,5]. Affected dogs manifest neurological signs of progressive motor dysfunction from 5–6 months of age and die at 12–18 months after a clearly defined clinical course [6,7], which is associated with progressive accumulation of GM1 ganglioside and the subsequent neuronal damage in the central nervous system [2,6,8]. …”

Characterization of Structural Connectivity of the Default Mode Network in Dogs using Diffusion Tensor Imaging

“…Furthermore, rabies has a long history of association with dogs and is almost never known to infect or to be transmitted to humans by small rodents such as rats, chipmunks or rabbits24. For these reasons dogs are an interesting species worth studying as animal models in translational research to study aging and its effect on disease progression as well as to investigate human diseases that affect white matter integrity such as neurological demyelinating conditions (e.g., Multiple Sclerosis)22, GM1 gangliosidosis, a fatal neurodegenerative lysosomal storage disease25 and Rabies, a virtually incurable disease26. Thus, non-invasive imaging of neural white matter tracts in the dog brain by using DTI could prove to be very useful.…”