Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat

Katayama, Kentaro; Sasaki, Takura; Goto, Syo; Ogasawara, Kei; Maru, Hiromi; Suzuki, Katsushi; Suzuki, Hiroyoshi

doi:10.1016/j.bone.2011.08.001

Cited by 38 publications

(45 citation statements)

References 47 publications

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“…Genomic PCR followed by Sanger sequencing confirmed that all three mutations were ENU induced and absent in the parental A/J and FVB/NJ strains. Because neither Itgb5 null mice nor Adcy5 null mice have palate defects (Huang et al, 2000;Iwamoto et al, 2003) and since ocd/ocd rats exhibit syndromic cleft palate associated with a Golgb1 disruption (Katayama et al, 2011), the Golgb1 ivs9+1G>A mutation became a prime candidate for causing cleft palate in the ENU1483 mice.…”

Section: G179smentioning

confidence: 99%

“…Mouse embryos deficient in p115 exhibit early embryonic lethality and Golgi fragmentation in trophoblast cells (Kim et al, 2012). Although no Golgb1 mutant mice have been reported, Katayama et al recently identified a 10-bp insertion in exon 13 of the Golgb1 gene in rats carrying a spontaneous osteochondrodysplasia (ocd) mutation (Katayama et al, 2011). The ocd homozygous mutant rats exhibit disproportionate dwarfism, systematic edema, cleft palate and neonatal lethality (Katayama et al, 2011), but whether these developmental defects are caused by loss of Golgb1 function has not been validated and the cellular functions of Golgb1 in vivo remain to be characterized.…”

Section: Introductionmentioning

confidence: 99%

“…Although no Golgb1 mutant mice have been reported, Katayama et al recently identified a 10-bp insertion in exon 13 of the Golgb1 gene in rats carrying a spontaneous osteochondrodysplasia (ocd) mutation (Katayama et al, 2011). The ocd homozygous mutant rats exhibit disproportionate dwarfism, systematic edema, cleft palate and neonatal lethality (Katayama et al, 2011), but whether these developmental defects are caused by loss of Golgb1 function has not been validated and the cellular functions of Golgb1 in vivo remain to be characterized. In this study, we identify a splice donor site mutation in the Golgb1 gene that completely co-segregates with a cleft palate phenotype in a new chemically induced mutant mouse line.…”

Section: Introductionmentioning

confidence: 99%

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Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

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Cleft palate is a common major birth defect for which currently known causes account for less than 30% of pathology in humans. In this study, we carried out mutagenesis screening in mice to identify new regulators of palatogenesis. Through genetic linkage mapping and whole exome sequencing, we identified a loss-of-function mutation in the Golgb1 gene that co-segregated with cleft palate in a new mutant mouse line. Golgb1 encodes a ubiquitously expressed large coiled-coil protein, known as giantin, that is localized at the Golgi membrane. Using CRISPR/Cas9-mediated genome editing, we generated and analyzed developmental defects in mice carrying additional Golgb1 loss-of-function mutations, which validated a critical requirement for Golgb1 in palate development. Through maxillary explant culture assays, we demonstrate that the Golgb1 mutant embryos have intrinsic defects in palatal shelf elevation. Just prior to the developmental stage of palatal shelf elevation in the wildtype littermates, Golgb1 mutant embryos exhibit increased cell density, reduced hyaluronan accumulation, and impaired protein glycosylation in the palatal mesenchyme. Together, these results demonstrate that, although it is a ubiquitously expressed Golgi-associated protein, Golgb1 has specific functions in protein glycosylation and tissue morphogenesis.

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Section: G179smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

et al. 2016

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“…Genome‐wide association studies revealed that one mutation in Golgb1 Y1212C (rs3732410) appeared to have a dominant effect: the overall significance of this variant with a reduced risk of ischemic stroke in all sickle cell anemia (SCA) patients with stroke against control SCA patients (OR = 0.27; 95% CI = 0.14–0.52) (Katayama et al. 2011). Cerebrovascular disease is perhaps the most devastating complication with SCA for younger patients.…”

Section: Discussionmentioning

confidence: 99%

“…2011). The Golgb1 rs3732410 mutation is a naturally occurring variant and associated with protection from ischemic stroke (Flanagan et al.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in three genes are associated with hemorrhagic stroke

Liu

Ge²,

Liu

et al. 2015

Brain and Behavior

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BackgroundMultiligand receptor for advanced glycation end products (RAGE), osteoprotegerin, and Golgb1 genes may be implicated in atherosclerosis and vascular diseases. Single nucleotide polymorphisms (SNPs) rs1035798 in RAGE gene, rs2073617 and rs2073618 in TNFRSF11B, and rs3732410 in Golgb1 will be investigated on whether there is an association with hemorrhagic stroke (HS) in Chinese population.MethodsA total of 600 subjects including 199 HS patients and 401 controls were assayed. These samples were divided into two groups: the ≤50 year and >50 year groups. Genotyping of SNPs was determined using the SEQUENOM MassARRAY matrix‐assisted laser desorption ionization–time‐of‐flight–mass spectrometry. The association between genotype and HS risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses.ResultsOur data showed that in the ≤50 year group, the rs1035798 major allele homozygote C/C in RAGE gene was associated with an increased risk of HS, while Golgb1 rs3732410 minor allele homozygote G/G was associated with a decreased risk of HS. In the >50 year group, the major allele homozygote G/G of rs2073618 was found to be associated with an increased risk of HS.ConclusionsThe polymorphisms rs1035798 of RAGE gene, rs2073618 of TNFRSF11B, and rs3732410 of Golgb1 might be involved in the risk of HS at different stage of ages.

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Translation of genome to glycome: role of the Golgi apparatus

et al. 2019

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Glycans are one of the four biopolymers of the cell and they play important roles in cellular and organismal physiology. They consist of both linear and branched structures and are synthesized in a nontemplated manner in the secretory pathway of mammalian cells with the Golgi apparatus playing a key role in the process. In spite of the absence of a template, the glycans synthesized by a cell are not a random collection of possible glycan structures but a distribution of specific glycans in defined quantities that is unique to each cell type (Cell type here refers to distinct cell forms present in an organism that can be distinguished based on morphological, phenotypic and/or molecular criteria.) While information to produce cell type‐specific glycans is encoded in the genome, how this information is translated into cell type‐specific glycome (Glycome refers to the quantitative distribution of all glycan structures present in a given cell type.) is not completely understood. We summarize here the factors that are known to influence the fidelity of glycan biosynthesis and integrate them into known glycosylation pathways so as to rationalize the translation of genetic information to cell type‐specific glycome.

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Insertional mutation in the Golgb1 gene is associated with osteochondrodysplasia and systemic edema in the OCD rat

Cited by 38 publications

References 47 publications

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Golgb1 regulates protein glycosylation and is crucial for mammalian palate development

Polymorphisms in three genes are associated with hemorrhagic stroke

Translation of genome to glycome: role of the Golgi apparatus

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