English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Thyroid hormone receptor α ( THRA)  gene mutations, via dominant negative mode, cause erythroid abnormalities in patients. Using mice expressing a dominant negative TRα1 mutant (TRα1PV;  Thra1    PV /+  mice), we showed that TRα1PV acted directly to suppress the expression of key erythroid genes, causing erythroid defects. The nuclear receptor corepressor 1 (NCOR1) was reported to mediate the dominant negative effects of mutated TRα1. However, how NCOR1 could regulate TRα1 mutants in erythroid defects  in vivo  is not known. In the present study, we crossed  Thra1    PV /+  mice with mice expressing a mutant  Ncor1  allele ( NCOR1ΔID ;  Ncor1    ΔID   mice). TRα1PV mutant cannot bind to NCOR1ΔID. The expression of NCOR1ΔID ameliorated abnormalities in the peripheral blood indices, and corrected the defective differentiation potential of progenitors in the erythroid lineage. The defective terminal erythropoiesis of lineage-negative bone marrow cells of  Thra1    PV /+  mice was rescued by the expression of NCOR1ΔID. De-repression of key erythroid genes in  Thra1    PV /+   Ncor1   Δ ID /Δ ID   mice led to partial rescue of terminal erythroid differentiation. These results indicate that the inability of TRα1PV to recruit NCOR1ΔID to form a repressor complex relieved the deleterious actions of TRα1 mutants  in vivo . NCOR1 is a critical novel regulator underpining the pathogenesis of erythroid abnormalities caused by TRα1 mutants.

NCOR1 modulates erythroid disorders caused by mutations of thyroid hormone receptor α1