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Göteborgs universitets publikationer

Retardation of post-natal development caused by a negatively acting thyroid hormone receptor alpha1.

Författare och institution:
Alexander Tinnikov (-); Kristina Nordström (-); Peter Thorén (-); Jenny Kindblom (Institutionen för invärtesmedicin); Stephen Malin (-); Björn Rozell (-); Maria Adams (-); Odelia Rajanayagam (-); Sven Pettersson (-); Claes Ohlsson (Institutionen för invärtesmedicin, Avdelningen för internmedicin); Krishna Chatterjee (-); Björn Vennström (-)
Publicerad i:
The EMBO journal, 21 ( 19 ) s. 5079-87
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Most patients with the syndrome resistance to thyroid hormone (RTH) express a mutant thyroid hormone receptor beta (TRbeta) with transdominant negative transcriptional effects. Since no patient with a mutant TRalpha has been identified, we introduced a point mutation into the mouse thyroid hormone receptor (TRalpha1) locus originally found in the TRbeta gene, that reduces ligand binding 10-fold. Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. Homozygous mice died before 3 weeks of age. Adult heterozygotes overcome most of these defects except for cardiac function abnormalities, suggesting that other factors compensate for the receptor defect. However, the additional deletion of the TRbeta gene in this mouse strain caused a 10-fold increase in serum thyroxine, restored hormonal regulation of target genes for TRs, and rescued the growth retardation. The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Arginine, Cytosine, Disease Models, Animal, Flow Cytometry, Genes, Dominant, Genome, Growth, genetics, Humans, Mice, Point Mutation, Thyroid Hormone Receptors alpha, genetics, physiology
Postens nummer:
Posten skapad:
2008-10-14 09:30
Posten ändrad:
2010-01-26 11:04

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