DIFFERENTIAL EXPRESSION OF RAT AND HUMAN TYPE-1 METABOTROPIC GLUTAMATE-RECEPTOR SPLICE VARIANT MESSENGER-RNAS

The type I metabotropic glutamate receptor (mGlu(1)) messenger RNA and protein are known to be widely expressed in rat brain, but knowledge of the regional expression of splice variants other than mGlu(1a) is l imited. Probes were designed for in situ hybridization that specifical ly recognize each of the carboxy-terminal splice variants mGlu(1a), -( 1b), -(1c) and -(1d). The novel rat mGlu(1d) sequence was obtained by polymerase chain reaction and the predicted protein is highly homologo us to the human sequence but contains both conservative and radical su bstitutions and is slightly longer (912 vs 908 amino acids). Each rat mGlu(1) splice variant messenger RNA was found in a unique expression pattern. The messenger RNA encoding mGlu(1a) was abundant in cerebella r Purkinje cells and in mitral and tufted cells of the olfactory bulb. Strong expression was also detected in hippocampal interneurons, and neurons of the thalamus and substantia nigra, while moderate expressio n was found in colliculi and cerebellar granule cells. The mGlu(1b) me ssenger RNA was strongly expressed in Purkinje cells, hippocampal pyra midal neurons, dentate gyrus granule cells and lateral septum, and mod erately expressed in striatal, superficial cortical and cerebellar gra nule neurons. The mGlu(1d) messenger RNA was expressed in all regions where mGlu(1a) and -(1b) were detected; abundant in Purkinje cells, mi tral and tufted cells, and hippocampal principal neurons and interneur ons, strong in thalamus and substantia nigra, and moderate in lateral septum, cortex, striatum and colliculi. Human mGlu(1) splice variant e xpression in the cerebellum matched that found for the rat. No specifi c signal was found with a probe capable of hybridizing to the rat mGlu (1c) splice junction, although another probe designed against a more 3 ' sequence of mGlu(1c) gave strong signals in the cerebellum and hippo campus, and moderate signals in thalamus and colliculi. It is conclude d that mGlu(1d) messenger RNA is widely expressed, that mGlu(1a) and - (1b) messenger RNAs are expressed in almost complementary patterns and that formation of the mGlu(1c) splice junction is a rare event. (C) 1 998 IBRO. Published by Elsevier Science Ltd.