GM1-gangliosidosis in American black bears: Clinical, pathological, biochemical and molecular genetic characterization

Sureshkumar Muthupalani, Paola A. Torres, Betty C. Wang, Bai Jin Zeng, Samuel Eaton, Ildiko Erdelyi, Rebecca Ducore, Rajanikarath Maganti, John Keating, Bain J. Perry, Florina S. Tseng, Nicole Waliszewski, Mark Pokras, Robert Causey, Rita Seger, Philip March, Amy Tidwell, Rolf Pfannl, Thomas Seyfried, Edwin H. KolodnyJoseph Alroy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

GM1-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal β-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from GM1-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a GM1-mouse. The bears presented at ages 10-14months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T2-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid β-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with GM1-ganglioside predominating. GA1 content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the GM1-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the GM1 mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T1042 to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with GM1-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population.

Original languageEnglish (US)
Pages (from-to)513-521
Number of pages9
JournalMolecular Genetics and Metabolism
Volume111
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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GM1 Gangliosidosis
Ursidae
Molecular Biology
Brain
Galactosidases
Gangliosides
Liver
Neurons
Complementary DNA
Genes
Cerebrosides
Sulfoglycosphingolipids
G(M1) Ganglioside
Lipids
Membrane structures
Mutation
Macrophages
N-Acetylneuraminic Acid
Fibroblasts
Chondrocytes

Keywords

  • American black bear
  • GLB1 gene
  • Neuronal storage
  • Y348H mutation
  • β-Galactosidase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

GM1-gangliosidosis in American black bears : Clinical, pathological, biochemical and molecular genetic characterization. / Muthupalani, Sureshkumar; Torres, Paola A.; Wang, Betty C.; Zeng, Bai Jin; Eaton, Samuel; Erdelyi, Ildiko; Ducore, Rebecca; Maganti, Rajanikarath; Keating, John; Perry, Bain J.; Tseng, Florina S.; Waliszewski, Nicole; Pokras, Mark; Causey, Robert; Seger, Rita; March, Philip; Tidwell, Amy; Pfannl, Rolf; Seyfried, Thomas; Kolodny, Edwin H.; Alroy, Joseph.

In: Molecular Genetics and Metabolism, Vol. 111, No. 4, 2014, p. 513-521.

Research output: Contribution to journalArticle

Muthupalani, S, Torres, PA, Wang, BC, Zeng, BJ, Eaton, S, Erdelyi, I, Ducore, R, Maganti, R, Keating, J, Perry, BJ, Tseng, FS, Waliszewski, N, Pokras, M, Causey, R, Seger, R, March, P, Tidwell, A, Pfannl, R, Seyfried, T, Kolodny, EH & Alroy, J 2014, 'GM1-gangliosidosis in American black bears: Clinical, pathological, biochemical and molecular genetic characterization', Molecular Genetics and Metabolism, vol. 111, no. 4, pp. 513-521. https://doi.org/10.1016/j.ymgme.2014.02.002
Muthupalani, Sureshkumar ; Torres, Paola A. ; Wang, Betty C. ; Zeng, Bai Jin ; Eaton, Samuel ; Erdelyi, Ildiko ; Ducore, Rebecca ; Maganti, Rajanikarath ; Keating, John ; Perry, Bain J. ; Tseng, Florina S. ; Waliszewski, Nicole ; Pokras, Mark ; Causey, Robert ; Seger, Rita ; March, Philip ; Tidwell, Amy ; Pfannl, Rolf ; Seyfried, Thomas ; Kolodny, Edwin H. ; Alroy, Joseph. / GM1-gangliosidosis in American black bears : Clinical, pathological, biochemical and molecular genetic characterization. In: Molecular Genetics and Metabolism. 2014 ; Vol. 111, No. 4. pp. 513-521.
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