Effects of 2,3-DPG knockout on SCD phenotype in Townes SCD model mice.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
07
08
2023
received:
14
04
2023
accepted:
21
08
2023
medline:
16
11
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
ppublish
Résumé
Sickle cell disease (SCD) is a severe, multisystemic hematological disorder that impacts nearly every major organ in adults. The current approved treatments for SCD directly target mutant hemoglobin or address downstream disease pathology. Several compounds targeting reduction of 2,3-DPG by activation of Pyruvate Kinase-R are currently being evaluated in SCD patients. In this study, we genetically engineered a mouse lacking 2,3-DPG on the Townes SCD mouse model background and evaluated the effects of 2,3-DPG loss on disease pathology. Animals lacking 2,3-DPG showed improvements in hematological markers and reductions in RBC sickling relative to native Townes mice, however, minimal difference in organ damage was observed in 2,3-DPG deficient mice compared to native Townes animals. When animals lacking 2,3-DPG were dosed with a compound designed to increase hemoglobin oxygen affinity, oxygen delivery related toxicity was observed.
Substances chimiques
2,3-Diphosphoglycerate
138-81-8
Hemoglobins
0
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1838-1846Informations de copyright
© 2023 Wiley Periodicals LLC.
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