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Journal of Neuroscience, Vol 14, 1141-1152, Copyright © 1994 by Society for Neuroscience
Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions
LT O'Connor, JC Lauterborn, CM Gall and MA Smith
Department of Anatomy and Neurobiology, University of California at Irvine 92717.
Agrin is a protein implicated in the formation and maintenance of the
neuromuscular junction. In addition to motor neurons, agrin mRNA has been
detected in the brains of embryonic rat and chick and adult marine ray,
suggesting that this molecule may also be involved in the formation of
synapses between neurons. As a step toward understanding agrin's role in
the CNS, we utilized Northern blot and in situ hybridization techniques to
analyze the regional distribution and cellular localization of agrin mRNA
in the spinal cord and brain of adult rats. The results of these studies
indicate that the agrin mRNA is expressed predominantly by neurons broadly
distributed throughout the adult CNS. Moreover, expression of agrin mRNA is
not restricted to cholinergic structures or regions of the brain receiving
cholinergic input. Recently, RNA isolated from rat embryonic spinal cord
was shown to contain four alternatively spliced agrin mRNAs, referred to as
agrin0, agrin8, agrin11, and agrin19, each of which encodes agrin proteins
that are active in acetylcholine receptor aggregating assays (Ferns et al.,
1992). Using the polymerase chain reaction we demonstrate that all four of
these agrin transcripts are expressed within the adult CNS. Agrin0, agrin8,
and agrin19 were present in all regions analyzed. In contrast, agrin11 was
detected only in forebrain. Results of these studies indicate that both the
level of expression and pattern of alternative splicing of agrin mRNA are
differentially regulated in the brain. The broad and predominantly neuronal
distribution of agrin mRNA in the adult brain suggests that, in addition to
its role at the neuromuscular junction, agrin may play a role in formation
and maintenance of synapses between neurons in the CNS.
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