Control of transcription in the RORa-staggerer mutant mouse cerebellum: glutamate receptor delta2 mRNA.
The staggerer (transcription factor RORa-deleted) mutation blocks cerebellar Purkinje cell development shortly after birth. In double mutants, the homozygous staggerer mutation can 'rescue' Purkinje cells carrying a channel-opening mutation in the Glutamate receptor delta2 (Lurcher) from apoptotic death during the third and fourth postnatal weeks. Transcript levels for the glutamate receptor delta2, a channel subunit that is found at both climbing fiber and parallel fiber synapses on cerebellar Purkinje cells, are higher in the staggerer mutant cerebellum than in the wild-type cerebellum at age 14 days. By 21 days, the wild-type level is higher, having increased tremendously while the staggerer increase is modest. The results imply that the mechanism protecting Purkinje cells in staggerer-Lurcher double mutants operates by blocking mutant receptor protein localization, rather than mRNA transcription. Between the ages 10 and 14 days, the climbing fiber innervation of Purkinje cells is known to switch from multiple to single in wild-type, but not in the staggerer mutant. Therefore, the results also suggest that the multiple innervation and the level of the receptor message are coordinated, either directly or indirectly.
Messer
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Wadsworth Center, New York State Department of Health, David Axelrod Institute, PO Box 22002, Albany, NY 12201-2002, USA. messer@wadsworth.org
Kang
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D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics*
D012333:RNA, Messenger; D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2