PuSH - Publikationsserver des Helmholtz Zentrums München: Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase deficiency.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Segal, J.* ; Mülleder, M.* ; Krüger, A.* ; Adler, T. ; Scholze-Wittler, M.* ; Becker, L. ; Calzada-Wack, J. ; Garrett, L. ; Hölter, S.M. ; Rathkolb, B. ; Rozman, J. ; Rácz, I. ; Fischer, R. ; Busch, D.H.* ; Neff, F. ; Klingenspor, M.* ; Klopstock, T.* ; Grüning, N.M.* ; Michel, S.* ; Lukaszewska-McGreal, B.* ; Voigt, I.* ; Hartmann, L.* ; Timmermann, B.* ; Lehrach, H.* ; Wolf, E.* ; Wurst, W. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Schrewe, H.* ; Yuneva, M.* ; Ralser, M.*

Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase deficiency.

J. Inherit. Metab. Dis. 42, 839-849 (2019)

Postprint

Forschungsdaten

DOI

PMC

	Open Access Green

Abstract
Metriken
Zusatzinfos

Triosephosphate isomerase (TPI) deficiency is a fatal genetic disorder characterized by hemolytic anemia and neurological dysfunction. Although the enzyme defect in TPI was discovered in the 1960s, the exact etiology of the disease is still debated. Some aspects indicate the disease could be caused by insufficient enzyme activity, whereas other observations indicate it could be a protein misfolding disease with tissue-specific differences in TPI activity. We generated a mouse model in which exchange of a conserved catalytic amino acid residue (isoleucine to valine, Ile170Val) reduces TPI specific activity without affecting the stability of the protein dimer. TPIIle170Val/Ile170Val mice exhibit an approximately 85% reduction in TPI activity consistently across all examined tissues, which is a stronger average, but more consistent, activity decline than observed in patients or symptomatic mouse models that carry structural defect mutant alleles. While monitoring protein expression levels revealed no evidence for protein instability, metabolite quantification indicated that glycolysis is affected by the active site mutation. TPIIle170Val/Ile170Val mice develop normally and show none of the disease symptoms associated with TPI deficiency. Therefore, without the stability defect that affects TPI activity in a tissue-specific manner, a strong decline in TPI catalytic activity is not sufficient to explain the pathological onset of TPI deficiency.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

4.287

1.498