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

Daisuke Hasegawa,Yuya Nakamoto,Shunta Mizoguchi,Osamu Yamato,Akira Yabuki,Tsuyoshi Ozawa,Takayuki Kuwabara,Kazuhito Itamoto,Hiromitsu Orima,Michio Fujita,Kimimasa Takahashi

doi:10.1100/2012/250197

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.

Highlights

GM1 gangliosidosis is a lysosomal storage disease caused by autosomal recessively inherited deficiency of β-galactosidase enzyme activity due to the mutations of GLB1 gene [2]
T2W and FLAIR hyperintensity in the subcortical white matter of the whole cerebrum was consistently observed on all images of the dogs affected with GM1 gangliosidosis regardless of timepoint (Figures 1(B), 1(C), and 2)
This finding was discovered using multiple MR imaging systems that ranged from 0.3 to 1.5 Tesla, the images obtained with a 1.5-Tesla system more clearly demonstrated this abnormal finding (Figure 1(B)), while the FLAIR images obtained with a 0.3-Tesla system were not as clear (Figure 1(C))

Summary

Introduction

GM1 gangliosidosis is a lysosomal storage disease caused by autosomal recessively inherited deficiency of β-galactosidase enzyme activity due to the mutations of GLB1 gene [2]. The disease has been detected in mixed-breed beagles [3], English Springer Spaniels (ESSs) [4], Portuguese water dogs (PWDs). [5], Alaskan huskies [6], Shiba Inu dogs (SIDs) [7], and a mixed-breed dog [8]. The molecular defects that cause the disease have been identified in PWDs [9], Alaskan huskies [10], and SIDs [11]. These molecularly defined canine models are expected to provide versatile in vivo systems for testing newly developed therapeutic strategies such as gene and regeneration therapies

Methods

Results

Conclusion