Beta receptor isoforms are not essential for thyroid hormone-dependent acceleration of PCP-2 and myelin basic protein gene expression in the developing brains of neonatal mice.
In rat pups, thyroid hormone dependent brain development coincides with the appearance of the thyroid hormone receptor (TR)beta1 isoform. This finding led to the suggestion that TRbeta1 plays an essential role in brain development. The recent availability of a mouse TRbeta knockout strain allowed us to test this possibility by determining whether TRbeta is essential for the normal developmental pattern of expression of two thyroid hormone regulated brain genes, myelin basic protein (MBP), and Purkinje cell protein 2 (Pcp-2). Northern analysis of total mRNA from the brains of wild-type mice established that, as in the rat pup, the initial rate of rise of the MBP and Pcp-2 mRNA is slowed in the hypothyroid state. Supporting the effectiveness of TRbeta gene deletion was the finding that the thiiodothyronine (T3) nuclear binding capacity in the livers and brains of knockout animals was consistent with the fractional contribution of TRbeta1 to total binding capacity in the wild-type tissues. Further, no TRbeta1 could be detected by isoform-specific immunoprecipitation of nuclear receptor extracts. However, deletion of the functional TRbeta in the TRbeta knockout mice did not affect the normal ontogeny of expression of the Pcp-2 and MBP genes in the postnatal pup. We conclude that TRbeta is not essential for the normal developmental expression of these T3 dependent brain genes.
Sandhofer
C
C
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Schwartz
H L
HL
Mariash
C N
CN
Forrest
D
D
Oppenheimer
J H
JH
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D010641:Phenotype; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; D004676:Myelin Basic Protein; D009479:Neuropeptides; C104971:Pcp2 protein, mouse; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine