Elsevier

Gene Expression Patterns

Volumes 25–26, November 2017, Pages 36-45
Gene Expression Patterns

Characterization of Sgo1 expression in developing and adult mouse

https://doi.org/10.1016/j.gep.2017.04.004Get rights and content

Abstract

SGO1 has been characterized in its function in correct cell division and its role in centrosome cohesion in the nucleus. However, its organ-specific maturation-related expression pattern in vivo remains largely uncharacterized. Here, we show clear SGO1 expression in post-developmental neuronal cells and cytoplasmic localisation in nucleated cells with a transgenic mice model and immunohistochemistry of wild type mice. We demonstrate extranuclear expression of Sgo1 in the developing heart and gut, which have been shown to be dysregulated in humans with homozygous SGO1 mutation. Additionally, we show Sgo1 expression in select population of retinal cells in developing and post-developmental retina. Our expression analysis strongly suggests that the function of SGO1 goes beyond its well characterized role in cell division.

Introduction

At the prophase of animal cell division, sister chromatids are held together with centromeric protein complex called cohesin until the chromatids are separated by the spindle apparatus at metaphase. Shugoshin-1 (SGO1), is a member of the cohesin protein complex and prevents the removal of this cohesin ring until the end of metaphase. Depletion of SGO1 in Hela cells causes premature loss of centromeric cohesin, precocious segregation of sister chromatids, and mitotic arrest (McGuinness et al., 2005). Mice haploinsufficient for Sgo1 are fertile and viable, but develop a propensity towards colon tumors due to chromosomal instability (Yamada et al., 2012). Similar findings have been made in humans: somatic mutations of SGO1 have been identified in colon cancer and downregulation of SGO1 has been associated with chromosomal instability (Iwaizumi et al., 2009, Kahyo et al., 2011) demonstrating the significant role of SGO1 in cell division.

Interestingly, a rare non-synonymous mutation of SGO1 in humans has been shown to cause a generalized pacemaking disorder specifically affecting heart and gut rhythm termed Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome. Patients affected with CAID syndrome present with clinically significant sinoatrial node dysfunction (“sick sinus syndrome”) and chronic intestinal pseudo obstruction at an age between 5 and 40. More precisely, CAID syndrome is caused by a recessive missense mutation of a highly conserved amino-terminal lysine residue to glutamic acid (K23E). Knockdown of sgo1 in zebrafish causes bradycardia, a characteristic of a sick sinus syndrome seen in CAID (Chetaille et al., 2014).

The organ-specificity and the untimely early onset of electrophysiological symptoms of CAID syndrome patients prompted us to characterize Sgo1 expression pattern during mouse development with a focus on the affected organs. With a Sgo1-lacZ-knock-in mouse model and immunohistochemistry of wild type mice, we here show noteworthy Sgo1 expression in heart, gut, eye and other central nervous system tissue during development and post-development. The study furthermore demonstrates Sgo1 localisation in cytoplasmic region in nucleated cells in select organs.

Section snippets

Sgo1 expression is pervasive in early development and most robust in the developing heart and eye

Sgo1+/LacZ mice (het) were generated using the tm1a gene trap vector. In Sgo1+/LacZ mice, the tm1a was inserted between exon4 and 5 of Sgo1 (Fig. 1). Thus, the expression of lacZ is under the control of the endogenous locus, allowing assessment of Sgo1 expression using X-gal staining. This mouse model also contains multicistronic elements flanking the LacZ sequence which results in separate translation products of truncated N-terminal SGO1 and β-galactosidase. Sgo1 LacZ/LacZ mice were embryonic

Discussion

In this study, we aimed to analyze Sgo1 expression in developing mouse embryos in the context of organ-specific arrhythmic manifestations of the CAID syndrome which is caused by SGO1 mutations in humans. Based on the results shown above, three key observations stand: first, Sgo1 expression is more ubiquitous during development than the organ-specific phenotype of CAID syndrome suggests; second, intracellular localisation of SGO1 differs with tissue and cell type; and third, Sgo1 is expressed

Methods

Refer to Data in Brief (DiB, Song et al., 2017) article for the methods.

Acknowledgement

G.A. is the recipient of a Senior Clinical Research Scholar of the Fonds de Recherche du Québec – Santé. Funding for this study provided by the Canadian Institutes of Health Research to G.A. and S.N. and the Banque Nationale Research Chair in Cardiovascular Genetics to G.A. Additional funding was provided by the Canadian Institutes of Health Research and the Fonds de Recherche du Québec through the E-RARE initiative CoHEART. We thank Dr. Alyson Fournier's lab for the TUBB3 and RBPMS antibodies

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