Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons.

Perturbation of the homeostasis between proteases and their inhibitors has been associated with lesion-induced or degenerative neuronal changes. Protease nexin-1 (PN-1), a secreted serine protease inhibitor, is constitutively expressed in distinct neuronal cell populations of the adult CNS. In an earlier study we showed that transgenic mice with ectopic or increased expression of PN-1 in postnatal neurons have altered synaptic transmission.

Effects of maternal thyroid status on thyroid hormones and growth in congenitally hypothyroid goat fetuses during the second half of gestation.

Congenital hypothyroidism in Dutch goats is due to a thyroglobulin (TG) synthesis defect that is inherited in an autosomal recessive manner. Minute amounts of mutated TG messenger RNA are translated into glycosylated TG fragments that contain the N-terminal hormonogenic site and are able to form T4, albeit less efficiently. We analyzed the effects of maternal thyroid status on fetal plasma thyroid hormones and growth during the second half of gestation (E90-E150).

Effect of thyroid hormone deficiency on RC3/neurogranin mRNA expression in the prenatal and adult caprine brain.

Thyroid hormone deficiency has profound effects on the brain during development and less marked effects on the adult brain. These effects are considered to be the result of the direct regulation of specific target genes by thyroid hormone. Previous studies have shown that the expression of the neuronal gene RC3, encoding a 78-amino-acid calmodulin-binding protein kinase C substrate, is under the influence of thyroid hormone in vivo.

Caprine homologue of rodent 5'-AMP-activated protein kinase subunit and yeast SNF4/CAT3 is down-regulated by thyroid hormone.

We isolated a cDNA, B12, that was down-regulated by thyroid hormone (TH) in the goat cerebellum, using a polymerase chain reaction (PCR)-based subtractive hybridization and differential screening procedure. Northern blot analysis of RNA from cerebellum of T4-treated and untreated hypothyroid goats confirmed that clone B12 was TH-regulated with an average reduction in expression of 21% after 4 days of T4 supplementation. Other tissues from a T4-treated and an untreated hypothyroid goat also revealed down-regulation of B12, with the highest reduction in expression found in the thyroid gland (38%).

RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism.

In view of the profound effects of thyroid hormone deficiency on the central nervous system (CNS), neuronal genes regulated by thyroid hormone could potentially be involved in the development of the CNS. Expression of the neuronal gene RC3/neurogranin was shown to be induced by thyroid hormone in the rat. No data are available on RC3 expression in mammals with prenatal brain development, like humans.