ADAMTSL4
- Known as:
- ADAMTSL4
- Catalog number:
- 001176A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ADAMTSL4
Related genes to: ADAMTSL4
- Gene:
- ADAMTSL4 NIH gene
- Name:
- ADAMTS like 4
- Previous symbol:
- TSRC1
- Synonyms:
- DKFZP434K1772
- Chromosome:
- 1q21.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-06-02
- Date modifiied:
- 2015-11-09
Related products to: ADAMTSL4
Related articles to: ADAMTSL4
- Congenital ectopia lentis (CEL) is a rare pediatric ocular disorder characterized by zonular fiber defects leading to lens dislocation and is genetically heterogeneous. Among known causes, biallelic mutations in ADAMTSL-4 represent the second most common genetic contributor, frequently associated with ectopia pupillae (EP)-a distinct and clinically significant feature. However, the mechanisms by which ADAMTSL-4 mutations lead to these ocular abnormalities remain poorly understood, partly due to the lack of effective animal models. In this study, we generated adamtsl-4 knock-out zebrafish lines using the CRISPR/Cas9 system. Through microinjection of sgRNA/Cas9 complexes and multigenerational screening, we established stable homozygous mutant lines. These mutants exhibited consistent phenotypes, including lens dislocation into the vitreous body and marked pupillary displacement, faithfully recapitulating human ADAMTSL-4-related EL and EP. This method provides a practical and scalable strategy for generating loss-of-function zebrafish models, with demonstrated utility in recapitulating phenotypes associated with ADAMTSL-4 mutations. Our approach offers a valuable tool for investigating the molecular mechanisms underlying CEL and EP and may support drug screening and therapeutic discovery in the future. - Source: PubMed
Chen ZexuHuang XinyiPi YanJiang Yongxiang - The ADAMTS family are extracellular matrix (ECM) proteins and enzymes involved in regulating tissue structure and function. The ECM is a network of proteins and polysaccharides surrounding the cells that provide support and maintain cellular function. Mutations to proteins in the ECM lead to systemic connective tissue disorders by disrupting the structural integrity and maintenance of the ECM, resulting in ocular, musculoskeletal, skin, and cardiovascular abnormalities. Mutations that arise from the ADAMTS family lead to specific connective tissue disorders with distinct clinical characteristics. Here, we detail these distinct clinical features of major connective tissue disorders that arise from mutations in the ADAMTS family proteins. These include Ehlers Danlos syndrome arising from mutation in , Geleophysic Dysplasia from 2, Weill-Marchesani Syndrome from and , Ectopia lentis from , thoracic aortic aneurysms and dissection from , valvular disease in , and a further connective tissue disorder from mutations in This review details the mechanisms in which mutations to these genes impair the structure of the ECM, leading to the variety of phenotypic outcomes seen in connective tissue disorders. - Source: PubMed
Publication date: 2026/03/31
Alcocer Ana DRush Elizabeth HMead Timothy J - Glioblastoma multiforme (GBM) is a heterogeneous and malignant brain tumor characterized by an immunosuppressive microenvironment, notably with diminished M1 macrophage activity. MicroRNAs serve as post-transcriptional regulators and have been implicated in influencing tumor progression. However, the interaction between microRNAs and tumor-associated macrophages in glioma remains less characterized. CCAAT/enhancer-binding protein delta (CEBPD) could act as an oncogenic factor in GBM and regulate microRNA transcription, thereby impacting tumorigenesis. In this study, we demonstrated that glioma CEBPD directly binds to and activates the promoter regions of miR-4257 and miR-3156, located within the genes ADAMTSL4 and ANKRD30BP3, respectively. These microRNAs are transmitted via small extracellular vesicles (sEVs) and target macrophages, specifically binding to the 3'-untranslated regions (UTRs) of interleukin 12 (IL-12) p35 and p40 mRNAs, thereby reducing IL-12 transcription and expression in macrophages. Furthermore, our results show that sEV antisense miR-4257 and miR-3156 diminish the M1 macrophage phenotype. In animal models, co-inoculation of glioma cells with antisense miR-4257 and miR-3156 or CEBPD knockdown, along with M1 macrophages, leads to reduced tumor growth and enhanced M1 macrophage activation. These findings suggest that glioma CEBPD can contribute to immunosuppression by regulating miR-4257 and miR-3156, which target IL-12 in macrophages through sEV transmission. This research offers new insights into the relationship between glioma and immunosuppression, highlighting potential therapeutic avenues for enhancing anti-tumor immunity in GBM. - Source: PubMed
Publication date: 2026/02/25
Chu Yu-YiKo Chiung-YuanWang Shao-MingWang Wei-JanWang Chih-YangChen Feng-WeiLiang Hsin-YinWang Ju-Ming - Gliomas, and particularly glioblastoma (GBM), remain among the most lethal primary brain tumors, with outcomes constrained by extensive intra tumor heterogeneity, a profoundly immunosuppressive tumor microenvironment (TME), and the restrictive nature of the blood-brain barrier (BBB). Although immunotherapies, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T and NK cells, and oncolytic virotherapy, have redefined treatment paradigms in other malignancies, their efficacy in gliomas has been modest, limited by low tumor mutational burden, antigenic plasticity, metabolic suppression, and therapy-associated immunosuppression. Recent advances in multi-antigen targeting, metabolic reprogramming, and innovative delivery strategies have enhanced preclinical efficacy, while the integration of emerging biomarkers such as ADAMTSL4, ACSS3, and radiomics-derived immune signatures offers opportunities for precision patient stratification. Converging developments in real-time molecular monitoring, spatial immunoprofiling, and rationally designed combination regimens hold the potential to recalibrate the glioma immune landscape, paving the way toward clinically impactful and durable immunotherapeutic responses. - Source: PubMed
Publication date: 2026/01/08
Jabri AbdullahMhannayeh AbdulazizTaftafa BaderAlsharif MohamedSibai DaniaAlsharif RaghadAbbad TasnimElsalti AbdulrahmanAhmed ZaraSalma JahanKhan Mohammed ImranYaqinuddin Ahmed - Pathogenic variants in ADAMTSL4 are an important cause of isolated ectopia lentis with an increasing number of genetically confirmed cases internationally. We sought to better describe ocular features seen with pathogenic variants in ADAMTSL4. We performed a retrospective, multicenter study examining the phenotypic and genotypic spectrum of ADAMTSL4-associated ocular disease. We identified 41 individuals from 32 families with genetically confirmed ADAMTSL4-related disease across six tertiary referral centers across Europe. Identified participants had a young age of diagnosis (median 1.3 years) and a highly myopic refractive error (mean SE -10.27 D). A diagnosis of ectopia lentis et pupillae was made in a third of cases, with a younger age at diagnosis (median 0.5 years). Subluxation tended to be in the inferior direction (~33%). Zonules were noted to be missing or absent in the majority of cases. Sixteen different pathogenic variants in ADAMTSL4 were reported. A previously reported 20-bp deletion (c.767_786del) was highly prevalent in this cohort (23/32), and all ectopia lentis et pupillae cases carried this variant. ADAMTSL4-related disease tends to present at a younger age and be associated with higher myopia than other forms of ectopia lentis (such as FBN1). Early identification of typical phenotypic features alongside genetic testing can aid early, precise diagnosis and prevent unnecessary investigations. - Source: PubMed
Publication date: 2025/11/17
Williams Katie MBerger WolfgangKoller SamuelPfiffner Fatma KivrakMaspoli AlessandroGloggnitzer JiradetBrühwiler Britta V TStathopoulos ChristinaMunier FrancisAllen LouiseIosifidis ChristosBlack Graeme CSergouniotis Panagiotis ILloyd Ian ChristopherGerth-Kahlert Christina