E-viri
Recenzirano
Odprti dostop
-
Westermann, Lena Marie; Fleischhauer, Lutz; Vogel, Jonas; Jenei-Lanzl, Zsuzsa; Ludwig, Nataniel Floriano; Schau, Lynn; Morellini, Fabio; Baranowsky, Anke; Yorgan, Timur A; Di Lorenzo, Giorgia; Schweizer, Michaela; de Souza Pinheiro, Bruna; Guarany, Nicole Ruas; Sperb-Ludwig, Fernanda; Visioli, Fernanda; Oliveira Silva, Thiago; Soul, Jamie; Hendrickx, Gretl; Wiegert, J Simon; Schwartz, Ida V D; Clausen-Schaumann, Hauke; Zaucke, Frank; Schinke, Thorsten; Pohl, Sandra; Danyukova, Tatyana
Disease models & mechanisms, 11/2020, Letnik: 13, Številka: 11Journal Article
Mucolipidosis type III (MLIII) gamma is a rare inherited lysosomal storage disorder caused by mutations in encoding the γ-subunit of GlcNAc-1-phosphotransferase, the key enzyme ensuring proper intracellular location of multiple lysosomal enzymes. Patients with MLIII gamma typically present with osteoarthritis and joint stiffness, suggesting cartilage involvement. Using knockout ( ) mice as a model of the human disease, we showed that missorting of a number of lysosomal enzymes is associated with intracellular accumulation of chondroitin sulfate in chondrocytes and their impaired differentiation, as well as with altered microstructure of the cartilage extracellular matrix (ECM). We also demonstrated distinct functional and structural properties of the Achilles tendons isolated from and knock-in ( ) mice, the latter displaying a more severe phenotype resembling mucolipidosis type II (MLII) in humans. Together with comparative analyses of joint mobility in MLII and MLIII patients, these findings provide a basis for better understanding of the molecular reasons leading to joint pathology in these patients. Our data suggest that lack of GlcNAc-1-phosphotransferase activity due to defects in the γ-subunit causes structural changes within the ECM of connective and mechanosensitive tissues, such as cartilage and tendon, and eventually results in functional joint abnormalities typically observed in MLIII gamma patients. This idea was supported by a deficit of the limb motor function in mice challenged on a rotarod under fatigue-associated conditions, suggesting that the impaired motor performance of mice was caused by fatigue and/or pain at the joint.This article has an associated First Person interview with the first author of the paper.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.