Microarray analysis of knockout mice identifies cyclin D2 as a possible mediator for the action of thyroid hormone during the postnatal development of the cerebellum.
Thyroid hormone is a major regulator of postnatal brain development, but the precise molecular mechanisms underlying its action in this organ remain poorly understood. We used microarray analysis to identify new target genes in brain. Thyroid hormone treatment of hypothyroid Pax8(-/-) knockout mice, which lack thyroid follicular cells, had a very limited global effect on brain transcripts. This analysis mainly identified cyclin D2 as a new thyroid hormone target gene in the cerebellum of hypothyroid mice. Thyroid hormone receptor (TRalpha and/or TRbeta) knockout mice studies provided further genetic evidence that cyclin D2 is likely to mediate the antiapoptotic effect exerted by thyroid hormone on the cerebellum external granular layer neuroblasts but that this transcriptional activation is not directly exerted by the thyroid hormone receptors.
Poguet
Anne-Lise
AL
Laboratoire de Biologie Moléculaire et Cellulaire de l'Ecole Normale Supérieure de Lyon UMR CNRS 5665 LA INRA913, 46 Allée d'ltalie 69364 Lyon CEDEX07France.
Legrand
Claude
C
Feng
Xu
X
Yen
Paul M
PM
Meltzer
Paul
P
Samarut
Jacques
J
Flamant
Frédéric
F
D000818:Animals; D002531:Cerebellum / Q000254:growth & development*; D056742:Cyclin D2; D016213:Cyclins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D037021:Thyroid Hormone Receptors alpha / Q000502:physiology; D037042:Thyroid Hormone Receptors beta / Q000502:physiology; D013963:Thyroid Hormones / Q000494:pharmacology*
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones