ALPL siRNA_Lentivectors
- Known as:
- ALPL siRNA_Lentivectors
- Catalog number:
- i000882a
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ALPL siRNA_Lentivectors
Related genes to: ALPL siRNA_Lentivectors
- Gene:
- ALPL NIH gene
- Name:
- alkaline phosphatase, biomineralization associated
- Previous symbol:
- HOPS
- Synonyms:
- TNSALP, TNALP, TNAP
- Chromosome:
- 1p36.12
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2018-08-08
Related products to: ALPL siRNA_Lentivectors
Related articles to: ALPL siRNA_Lentivectors
- Hypophosphatasia (HPP) is a rare metabolic disorder caused by loss-of-function ALPL variants and characterized by heterogeneous skeletal and extra-skeletal manifestations. Although recent diagnostic criteria include ALPL variants, the diagnosis can be made based solely on clinical features. In adult-onset HPP, however, symptoms are often mild or nonspecific, including musculoskeletal symptoms and fatigue, making it difficult to differentiate from other conditions. This retrospective, cross-sectional study aimed to integrate genetic and biochemical data to enhance the clinical interpretation of low alkaline phosphatase (ALP) in patients with bone disorders. Among 865 consecutive adults visiting a bone-specialized outpatient department, patients with persistent hypophosphatasemia underwent ALPL sequencing. Clinical and biochemical characteristics were compared among three groups: biallelic or monoallelic variants with dominant-negative effect (DNE), monoallelic variants without DNE, and variant-negative individuals. Fifty-six patients (6.5%) showed persistent hypophosphatasemia. Two (0.2%) were compound heterozygotes, and 29 (3.4%) carried monoallelic variants without DNE. Clinical symptoms and secondary causes of hypophosphatasemia were similar between monoallelic without DNE and variant-negative patients, whereas serum ALP, urinary phosphoethanolamine (PEA), and plasma inorganic pyrophosphate (PPi) differed significantly. A model using thresholds of ALP < 35 IU/L, urinary PEA > 91 µmol/gCr, and plasma PPi > 1.96 µmol/L demonstrated high diagnostic performance for identifying patients with monoallelic variants without DNE. This study elucidated the complex clinical spectrum of patients with low ALP. Although clinical manifestations were comparable between monoallelic individuals without DNE and variant-negative individuals, distinct biochemical profiles were observed. Integrating genetic nosology into current diagnostic criteria may refine clinical decision-making. - Source: PubMed
Publication date: 2026/07/15
Hidaka NaokoKimura SoichiroWatanabe SoAkiyama TomoyukiTachikawa KanakoMichigami ToshimiAdachi NatsuhoIrie KokiHoshino YoshitomoKato HajimeNangaku MasaomiTanaka SakaeMakita NorikoSaito TakuIto Nobuaki - Calcium (Ca) and magnesium (Mg) ions enhance the osteoconductivity of titanium oral implants, yet their effects on clinically established complex topographies remain under-explored. This study evaluated the effects of Ca and Mg incorporation into sandblasted, large-grit-, acid-etched (SLA) surfaces on the osteogenic differentiation of human mesenchymal stem cells (MSCs). - Source: PubMed
Kim Jae-MinKim Young-KyungPark Jin-Woo - Hypophosphatasia (HPP) is a rare inherited metabolic bone disorder caused by pathogenic variants in the gene, with a wide clinical spectrum ranging from severe pediatric forms to mild adult-onset disease. In contrast, heterozygous variants in are a recognized cause of autosomal dominant short stature, often associated with advanced bone age and premature growth plate closure. We report a 16-yr-old girl evaluated for severe disproportionate short stature with growth arrest during early adolescence. Her medical history included benign childhood epilepsy, mild intellectual disability, and enamel abnormalities. Biochemical evaluation revealed persistently low serum and bone-specific alkaline phosphatase levels, while calcium-phosphate metabolism was otherwise normal. Genetic testing identified a heterozygous pathogenic variant (c.1426G>A; p.Glu476Lys), inherited from an asymptomatic father, consistent with autosomal dominant HPP with minimal clinical expression. Additionally, a maternally inherited variant of uncertain significance (c.511G>C; p.Ala171Pro) was detected. Based on phenotypic correlation and family segregation, the growth phenotype is more plausibly explained by -related growth plate dysfunction, while the variant likely represents an incidental or mildly expressed finding. This case highlights the importance of careful genotype-phenotype correlation and cautious interpretation of multiple genetic findings in the evaluation of severe short stature. - Source: PubMed
Publication date: 2026/02/15
Silva Joana AzevedoCosta Ana Rita AMazeda InêsMota CéuAbreu MariaBorges TeresaMendes Catarina - Inorganic pyrophosphate (PPi) is a key inhibitor of ectopic calcification, yet transcriptional regulation of genes controlling its systemic production and degradation (ABCC6, ALPL, ANKH, and ENPP1) remains poorly understood. We hypothesized that PPi homeostasis is regulated by an evolutionarily conserved transcription factor (TF) network. Promoter motif analysis combined with ATAC-seq revealed conserved enrichment of TF binding sites, including FOXA1, HNF4A, and SREBF1, across mouse and human orthologues. Bulk and single-cell RNA-seq together with RT-qPCR analyses in wild-type and Abcc6 mice showed hepatocytes as major cell type expressing the most relevant genes maintaining PPi homeostasis. Further inference analysis identifies a conserved transcriptional program that regulates systemic PPi balance across mice and humans. Functionally, mice showed an age-dependent inverse correlation between plasma PPi and serum alkaline phosphatase (AP) activity, strongest during early life. Abcc6 mice displayed persistently reduced but gradually increasing PPi levels and altered Pi/PPi ratios during aging. In humans, plasma PPi correlated inversely with AP activity and positively with Pi in both controls and ABCC6-deficient pseudoxanthoma elasticum patients. Together, these findings support a conserved TF-associated regulatory program linking PPi homeostasis gene expression with circulating mineralization-related factors across physiological and pathological states. - Source: PubMed
Publication date: 2026/07/10
Tamatey VirgilVárhegyi MartinBlaha BenceVan Wynsberghe JudithLion LonaAhmadi ZahiraJuhász DénesBata EmeseMárton Dániel TóthMuhyiddeen MuazuNagy Anikó IlonaMartinez-Jimenez Celia PVanakker OlivierArányi TamásSzeri Flóra - Recent advances in engineering adeno-associated virus (AAV) capsids capable of crossing the blood-brain barrier (BBB) have led to the development of numerous variants aimed at enhancing central nervous system gene delivery. Over the past decade, as new BBB-penetrant capsids were reported or independently identified through our own capsid library screening, we systematically evaluated their performance in adult marmosets, using a standardized experimental framework. Here, we present a cross-comparison of eleven AAV variants, predominantly AAV9-derived, alongside native AAV9 following systemic administration. Whole-brain reporter expression was quantitatively assessed using uniform imaging and analysis pipelines to enable relative comparison across animals. Under these conditions, most previously reported and newly identified BBB-penetrant variants-including those obtained through our own screening efforts-did not exhibit brain transduction levels clearly distinguishable from those of AAV9 based on whole-brain fluorescence intensity. In contrast, VCAP-102 consistently produced markedly higher brain-wide reporter expression across animals, accompanied by substantially increased vector genome copy numbers in the marmoset cortex, with most GFP-positive cells corresponding to neurons. These findings provide a systematic benchmark for evaluating BBB-penetrant AAV capsids in non-human primates and identify VCAP-102 as a highly efficient vector for systemic brain gene delivery. - Source: PubMed
Publication date: 2026/06/16
Matsuzaki YasunoriKonno AyumuSakamoto KenjiUchida YasuoTerasaki TetsuyaHirai Hirokazu