Glial fibrillary acidic protein mRNA isotypes: expression in vitro and in vivo

Glial fibrillary acidic protein (GFAP) and its mRNA, primarily expressed in astrocytes, are also expressed in peripheral nervous system Schwann cells as well as in certain non-neural tissues. Schwann cells express a GFAP mRNA (GFAP-beta) which differs from the CNS-type mRNA (GFAP-alpha) by the presence of an extended 5' untranslated region. We have developed a polymerase chain reaction assay which allows distinction of these two GFAP mRNAs, as well as quantitative analysis of their levels. In the cultured rat Schwannoma cell line RT4-D6, GFAP-beta was the major GFAP mRNA species, accounting for at least 75% of total GFAP (alpha + beta) mRNA. GFAP-beta was also detected in primary rat astrocyte cultures, where it constituted approximately 5% of the total GFAP mRNA, as well as in RNA samples prepared from normal rat cerebral cortex, and from hamster and human brain. In rat cortex, the temporal expression of GFAP-beta mRNA paralleled that of total GFAP mRNA, with plateau levels reached between postnatal days 15 and 20. In astrocyte cultures, the relative levels of GFAP-alpha and -beta mRNAs were differentially regulated by exposure to interferon-gamma (10 to 25 units/ml), which caused an increase in GFAP-beta levels while at the same time no change or a small decrease in total GFAP levels. In rat brain cortical slices, 4 hr exposure to 25 units/ml interferon-gamma decreased total GFAP mRNA levels over tenfold, while GFAP-beta levels were unaffected. These data indicate that a second form of the GFAP mRNA is expressed in astrocytes both in vivo and in vitro and provide evidence for independent regulation of these two GFAP mRNA species.