Down-regulation of two novel genes by hypoxic-ischaemic encephalopathy in neonatal mouse

Abstract

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neurologic deficit in neonates. Apoptosis is a key event triggered by HIE. To elucidate the cellular and molecular basis of HI-induced apoptosis, we adopted differential gene expression studies in 7-day-old C57Bl/6 mice HIE model, with permanent unilateral common carotid artery ligation plus 30 minutes of 8% O2/92% N2 hypoxia. Subtractive hybridization carried out between ipsilateral (to ligation) and contralateral brain hemispheres led to isolation of 87 differentially expressed genes in response to the HIE insult (43 and 44 are up- and down-regulated, respectively). Sequences of these products revealed about a quarter of them were homologous to known mouse genes and one-third were homologous to mouse EST sequences only and the other share various degree of homologies with cDNA of other species. HIE-Down-regulated gene (HID)-44 and -1 were two with partial sequences homologous with EST sequences. Northern analysis showed that the expression of these two genes were inhibited by 3 hours after HIE insult. Analysis of HID-44 showed that its mRNA was a 6-kb brain-specific transcript. However, mRNA of HID-1 was a 2-kb transcript expressed in most tissues, highest in testis followed by thymus and brain. Full-length cDNA of HID-44 and HID-1 genes were isolated from a mouse brain cDNA library and characterization of the full-length genes and their alteration in expression by HIE are currently ongoing. . Supported by Hong Kong Research Grant Council Fund HKU7249/99M to PT Cheung, HK Yip and MH Sham