Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration

Sheikh, Abdullah Md.; Yano, Shozo; Tabassum, Shatera; Omura, Koji; Araki, Asuka; Mitaki, Shingo; Ito, Yoshie; Huang, Shuai; Nagai, Atsushi

doi:10.3390/cells10010155

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Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration

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Department of Laboratory Medicine, Shimane University Faculty of Medicine, 89-1 Enya Cho, Izumo 693-8501, Japan

Department of Organ Pathology, Shimane University Faculty of Medicine, 89-1 Enya Cho, Izumo 693-8501, Japan

Department of Neurology, Shimane University Faculty of Medicine, 89-1 Enya Cho, Izumo 693-8501, Japan

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Department of Orthopedic Surgery, The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgangdong Road, Guangzhou 510260, China

Author to whom correspondence should be addressed.

Cells 2021, 10(1), 155; https://doi.org/10.3390/cells10010155

Received: 10 November 2020 / Revised: 9 January 2021 / Accepted: 11 January 2021 / Published: 14 January 2021

(This article belongs to the Collection The Pathogenesis of Neurological Disorders)

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Abstract

Ataxia and Male Sterility (AMS) is a mutant mouse strain that contains a missense mutation in the coding region of Nna1, a gene that encodes a deglutamylase. AMS mice exhibit early cerebellar Purkinje cell degeneration and an ataxic phenotype in an autosomal recessive manner. To understand the underlying mechanism, we generated neuronal stem cell (NSC) lines from wild-type (NMW7), Nna1 mutation heterozygous (NME), and Nna1 mutation homozygous (NMO1) mouse brains. The NNA1 levels were decreased, and the glutamylated tubulin levels were increased in NMO1 cultures as well as in the cerebellum of AMS mice at both 15 and 30 days of age. However, total β-tubulin protein levels were not altered in the AMS cerebellum. In NMO1 neurosphere cultures, β-tubulin protein levels were increased without changes at the transcriptional level. NMO1 grew faster than other NSC lines, and some of the neurospheres were attached to the plate after 3 days. Immunostaining revealed that SOX2 and nestin levels were decreased in NMO1 neurospheres and that the neuronal differentiation potentials were reduced in NMO1 cells compared to NME or NMW7 cells. These results demonstrate that the AMS mutation decreased the NNA1 levels and increased glutamylation in the cerebellum of AMS mice. The observed changes in glutamylation might alter NSC properties and the neuron maturation process, leading to Purkinje cell death in AMS mice. View Full-Text

Keywords: AMS mouse; NSC; deglutamylation; β-tubulin; MAP2; NNA1

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Sheikh, A.M.; Yano, S.; Tabassum, S.; Omura, K.; Araki, A.; Mitaki, S.; Ito, Y.; Huang, S.; Nagai, A. Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration. Cells 2021, 10, 155. https://doi.org/10.3390/cells10010155

AMA Style

Sheikh AM, Yano S, Tabassum S, Omura K, Araki A, Mitaki S, Ito Y, Huang S, Nagai A. Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration. Cells. 2021; 10(1):155. https://doi.org/10.3390/cells10010155

Chicago/Turabian Style

Sheikh, Abdullah M., Shozo Yano, Shatera Tabassum, Koji Omura, Asuka Araki, Shingo Mitaki, Yoshie Ito, Shuai Huang, and Atsushi Nagai. 2021. "Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration" Cells 10, no. 1: 155. https://doi.org/10.3390/cells10010155

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Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration

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