OCRL Mouse Monoclonal Antibody
- Known as:
- OCRL Mouse Monoclonal Antibody
- Catalog number:
- BIN-004952-M02
- Product Quantity:
- 0.1mg
- Category:
- -
- Supplier:
- Zyagen
- Gene target:
- OCRL Mouse Monoclonal Antibody
Related genes to: OCRL Mouse Monoclonal Antibody
- Gene:
- OCRL NIH gene
- Name:
- OCRL inositol polyphosphate-5-phosphatase
- Previous symbol:
- -
- Synonyms:
- OCRL1
- Chromosome:
- Xq26.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-01-22
Related products to: OCRL Mouse Monoclonal Antibody
Related articles to: OCRL Mouse Monoclonal Antibody
- Human brain development requires tight coordination of metabolic and signaling pathways. Lowe syndrome (LS) is a recessive X-linked disorder characterized by proximal tubular renal disease, congenital cataracts, glaucoma, and neurodevelopmental delays. While LS results from mutations in the gene, which encodes an inositol polyphosphate 5-phosphatase, the cellular mechanisms driving neuronal dysfunction remain poorly understood. In this study, using patient-derived iPSC neurons, an knockout mouse model, and an independent zebrafish OCRL-deficient model, we identified mitochondrial dysfunction as a conserved phenotype of OCRL loss across species. Collectively, our findings showed that OCRL deficiency leads to reduced mitochondrial activity, decreased mtDNA levels, reduced mitochondrial content (TOM20), and increased oxidative stress. We further showed that OCRL-deficient neural cells exhibited an altered balance of neuronal versus astrocytic differentiation, rather than a defect in neurogenesis. Additionally, we observed impaired Sonic Hedgehog (Shh) signaling and ciliary homeostasis. Thus, our findings support a model in which OCRL deficiency is associated with mitochondrial dysfunction, increased oxidative stress, altered neural lineage balance, and reduced Hedgehog pathway activity, providing a framework for understanding these interconnected phenotypes. - Source: PubMed
Publication date: 2026/09/18
Walkiewicz GrzegorzChen SiyuLo ChienhuiZhao JingyuLiu ZhiquanWang BiaoWang QingKowal Tia JLawson BenjaminSun Yang - Lowe syndrome is a rare, currently incurable multisystem disorder that affects the eyes, kidneys, and central nervous system. It is caused by mutations in the OCRL gene, which encodes an inositol 5-phosphatase. The disorder remains incurable, and the pathways underlying the ocular symptoms remain poorly understood, largely due to the lack of appropriate models. In this study, trabecular meshwork cell models of Lowe syndrome were generated to test two distinct gene therapy strategies: a mutation-agnostic OCRL DNA augmentation therapy and a patient-specific CRISPR-mediated gene correction strategy. The results showed that AAV2-OCRL demonstrated the highest transduction efficiency in patient iPSC-derived trabecular meshwork models (iHTM) among the three AAV-OCRL vectors evaluated, establishing it as a promising delivery vector. Targeted CRISPR-based gene therapy restored OCRL enzyme activity and corrected cellular defects in patient iPSC-derived trabecular meshwork cell models. Furthermore, RNA-sequencing analysis of these models revealed dysregulation of extracellular matrix organization, cell adhesion, focal adhesion, and cytoskeletal regulatory pathways, suggesting that disruption of interconnected ECM-adhesion-cytoskeletal networks may contribute to trabecular meshwork dysfunction in Lowe syndrome-associated glaucoma. These findings indicate the feasibility of OCRL gene augmentation and CRISPR-based gene editing in patient-derived ocular models and position AAV2-OCRL as a leading therapeutic candidate for Lowe syndrome. - Source: PubMed
Publication date: 2026/09/09
Chen SiyuLiu ZhiquanWang WenminWang QingKowal Tia JZhang FanWalkiewicz GrzegorzHossen FarukLachman Herbert MZhou JinqiongWang YitingSun Yang - Clinical co-occurrence of Parkinson's disease (PD) and age-related bone loss in elderly patients has garnered increasing attention, yet its molecular mechanisms remain incompletely elucidated. This study used an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in Ace2 mice to investigate the regulatory mechanisms of bone-brain axis-related genes and signaling pathways. Behavioral tests assessed motor and non-motor symptoms. Immunohistochemistry, Western blot, and histopathological staining analyzed dopaminergic neuron activity, microglial activation, and bone metabolic abnormalities. GEO dataset transcriptomics and weighted gene co-expression network analysis (WGCNA) identified key hub genes, with receiver operating characteristic (ROC) curves evaluating their diagnostic value in public single-disease transcriptome data. MPTP significantly exacerbated motor dysfunction and depression-like behaviors; Ace2 deletion lowered total Wnt, β-catenin, BMP and IGF-1 protein abundance alongside reduced phosphorylation ratios of their downstream kinases in brain and bone, while upregulating RANKL/RANK/OPG-associated inflammatory mediators, accompanied by elevated total α-synuclein, Casp3 and Bax protein levels. The parallel reduction of these signaling proteins only suggests potential perturbation of related cascades; WGCNA identified 10 hub genes (e.g., DNM1, OCRL, OPA1), whose dysregulation was linked to synaptic dysfunction and inflammation. ROC analysis based on single-disease datasets showed high diagnostic accuracy for PD and `osteoporosis (OP) (AUC: 0.683-0.981), with core genes influencing synaptic, MAPK, Rap1, and Ras pathways. These preclinical findings indicate that Ace2 deficiency is associated with concurrent pathological abnormalities in the brain and transient bone metabolic disturbance under short-term MPTP treatment in growing young male mice; coordinated dysregulation of shared signaling pathways was observed in the two tissues, consistent with a potential bone-brain axis pathological phenotype, though causal bidirectional tissue cross-talk cannot be confirmed in the current experimental design, providing candidate targets that warrant further validation. - Source: PubMed
Publication date: 2026/09/09
Liu TingtingRen YuhengTian XinghuaWei Jianshe - : To date, approximately 360 pathogenic variants of the gene have been reported, including frameshift, substitution, gross inversion, nonsense, and missense mutations. These genetic alterations have been associated with a broad phenotypic spectrum of Lowe syndrome, contributing to considerable variability in disease severity and clinical presentation. Missense variants are typically associated with preserved messenger RNA expression in fibroblasts, whereas more deleterious mutations result in markedly reduced expression of the transcript or protein product. Pathogenic variants in the gene have also been identified in patients with Dent's disease type 2. : This case report describes a pediatric male patient with autism spectrum disorder and renal dysfunction, who was found to harbor a variant of uncertain clinical significance in the gene and a pathogenic 16p11.2 chromosomal deletion. The patient, a 12-year-old boy with autism, presented with proteinuria during hospitalization for febrile gastroenteritis and streptococcal infection. Further evaluation revealed focal glomerulosclerosis, tubular calcium phosphate deposits, albuminuria, and hypercalciuria. Ophthalmologic examination additionally demonstrated bilateral lens opacities in the absence of congenital cataracts, as well as hyperopia. The coexistence of these clinical manifestations together with the identified gene variant raises the possibility of an atypical presentation of Dent disease type 2. Nevertheless, continued clinical and genetic follow-up remains warranted to further clarify the pathogenic significance of the detected variant and to establish a definitive diagnosis. : The uniqueness of this case resides in the coexistence of two independent genetic findings presenting a phenotype-attribution challenge. Furthermore, the identified phenotype may warrant consideration as a possible previously unreported phenotypic presentation situated along the clinical spectrum between Lowe syndrome and Dent disease type 2. The main contribution of this report is to illustrate the interpretative challenges of a concurrent pathogenic 16p11.2 deletion and an variant of uncertain significance in a patient with renal disease and neurodevelopmental features. - Source: PubMed
Publication date: 2026/07/17
Chronis ChristosStefanaki CharikleiaStergiou NikolaosKokkou EleniMakrythanasis PeriklisKosma KonstantinaTilemis Faidon-NikolaosTsouprou MariaTola ElonaFilippou OlgaBotsa Evanthia - Lowe syndrome (LS) is an X-linked disorder caused by OCRL mutations, encoding a phosphatidylinositol 5-phosphatase. OCRL regulates phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P]-dependent cytoskeletal dynamics and membrane trafficking in multiple cell types, including platelets. Clinically, LS manifests with cataracts, hypotonia, developmental delay, and progressive kidney disease. A subset of LS individuals shows bleeding tendency and occasional mild thrombocytopenia despite normal coagulation tests. Studies reveal impaired thrombus growth under flow, delayed platelet spreading on fibrinogen, abnormal clot retraction, and altered platelet formation with circulating barbell-shaped immature platelets, supporting a platelet dysfunction phenotype in LS, though exact molecular mechanisms remain undefined. Experimental studies suggest OCRL controls PI(4,5)P pools required for coordinated actin and microtubule remodeling during platelet adhesion and thrombopoiesis. Pharmacological OCRL inhibition recapitulates defective spreading, persistent filopodia, actin nodules, and impaired marginal microtubule band depolymerization without major loss of GPIb-IX-V or αIIbβ3 receptors, supporting a signaling and cytoskeletal mechanism. Elevated plasma fibrinogen, VWF, and FVIII in LS may partially offset bleeding, though their contribution to the LS phenotype and relationship to vascular/hepatic involvement remains unclear. Similarly, while the OCRL homolog INPP5B is abundant in platelets, its capacity to compensate for OCRL deficiency appears limited and requires further investigation. Recognition of this OCRL-dependent platelet phenotype has important clinical implications, including caution before surgical procedures and usage of medications that may worsen bleeding, highlighting the need for targeted diagnostic approaches and further mechanistic studies to improve the management of individuals with LS. - Source: PubMed
Publication date: 2026/07/02
Bura AnaJurak Begonja Antonija