Golga5 is dispensable for mouse embryonic development and postnatal survival

Abstract

Golgins are a family of coiled-coil proteins located at the cytoplasmic surface of the Golgi apparatus and have been implicated in maintaining Golgi structural integrity through acting as tethering factors for retrograde vesicle transport. Whereas knockdown of several individual golgins in cultured cells caused Golgi fragmentation and disruption of vesicle trafficking, analysis of mutant mouse models lacking individual golgins have discovered tissue-specific developmental functions. Recently, homozygous loss of function of GOLGA2, of which previous in vitro studies suggested an essential role in maintenance of Golgi structure and in mitosis, has been associated with a neuromuscular disorder in human patients, which highlights the need for understanding the developmental roles of the golgins in vivo. We report here generation of Golga5-deficient mice using CRISPR/Cas9-mediated genome editing. Although knockdown studies in cultured cells have implicated Golga5 in maintenance of Golgi organization, we show that Golga5 is not required for mouse embryonic development, postnatal survival, or fertility. Moreover, whereas Golga5 is structurally closely related to Golgb1, we show that inactivation of Golga5 does not enhance the severity of developmental defects in Golgb1-deficient mice. The Golga5-deficient mice enable further investigation of the roles and functional specificity of golgins in development and diseases.

The Physiological Functions of the Golgin Vesicle Tethering Proteins

“…There are orthologs of golgin-84 in D. melanogaster and C. elegans , although they have yet to be analyzed at the functional level. Mice lacking golgin-84, also known as GOLGA5, are viable, and there is no overt phenotype in these mice, which develop and grow normally (McGee et al, 2017). There is also no male infertility, indicating that golgin-84 is dispensable for acrosome biogenesis.…”

“…Loss of mammalian giantin, also called GOLGB1, in mouse knockout models, has revealed craniofacial defects, including a cleft palate (Lan et al, 2016; McGee et al, 2017). There is reduced accumulation of the matrix glycosaminoglycan (GAG) hyaluronan and reduced protein glycosylation, consistent with giantin functioning to maintain cargo protein glycosylation and GAG synthesis at the Golgi, which in turn is important for proper matrix assembly and formation of the palate (Lan et al, 2016).…”

“…Thus, although giantin is widely expressed throughout the body, the knockout phenotype is restricted to certain tissues. The combined knockout of giantin and golgin-84 gives the same phenotype as loss of giantin alone, arguing against the possibility that these golgins function in a redundant manner in vivo (McGee et al, 2017). In contrast to knockout mouse models, rats lacking giantin display a much more severe phenotype, manifesting as an embryonic lethal osteochondrodysplasia, with systemic oedema and shortening of the long bones in addition to craniofacial defects and a cleft palate (Katayama et al, 2011).…”

Giantin-knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression

“…Interestingly, chondrocytes from homozygous animals have expanded ER and Golgi membranes whilst cartilage growth plates contain less extracellular matrix (ECM), indicative of secretory pathway defects ( Katayama et al, 2011 ). Mouse giantin-KO models have less-complex developmental disorders, with the predominant phenotype being cleft palate ( Lan et al, 2016 ) and short stature ( McGee et al, 2017 ). These animals also have ECM abnormalities associated with glycosylation defects, but Golgi structure is normal ( Lan et al, 2016 ).…”

Golgi Complex Dynamics and Its Implication in Prevalent Neurological Disorders

“…Animal knockout (KO) models for Golgins such as Giantin or GMAP 210 have shown them to be essential for healthy development, as these animals exhibit defects in craniofacial and skeletal development (Smits et al, 2010; Stevenson et al, 2017). On the other hand, KO of Golgin-84, a protein closely related to Giantin, does not show any significant developmental abnormalities, and compound mutants for both of these Golgins do not show any additional defects (McGee et al, 2017). While these models highlight the importance of Golgins in embryonic development, some Golgins might be dispensable; indeed, several Golgins are associated with human diseases (Toh and Gleeson, 2016), but only a few have been linked to obvious neurological defects.…”