The transcription factor, Aplysia CCAAT enhancerbinding protein (ApC/EBP), plays a crucial role in long term facilitation, a synaptic mechanism of long term memory in Aplysia. To gain a clue to whether the mammalian C/EBP family of transcription factors are also involved in long term memory, we examined how C/EBP activities in hippocampal neurons can be modulated in response to cAMP and Ca 2؉ , crucial inductive signals for memory formation. As a result, stimulation of either cAMP or Ca 2؉ signals in hippocampal neurons was found to enhance mRNA expressions and DNA binding activities of C/EBP and C/EBP␦. Furthermore, it is indicated that CaM kinases have essential roles for increasing the expression and DNA binding activities of C/EBP in hippocampal neurons activated by membrane depolarization. Overexpression of constitutively active calcium/calmodulin-dependent kinase IV was found to directly stimulate either C/EBP-dependent or C/EBP␦-dependent transcription, reinforcing the evidence that C/EBP family members contribute to Ca 2؉ -dependent transcription. Thus, these results suggest that C/EBP and C/EBP␦ may be involved in the transcription-dependent phase of memory formation by increasing the expression of both the DNA binding and the transcriptional activities under the direction of cAMP and/or Ca 2؉ signaling in hippocampal neurons.
We found that la is located in linkage group XVIII. It is highly probable that la and tg are alleles, and closely, linked to Es-1. Mice of the genotype la/tg are abnormal, with clinical signs similar to tg, although more severe. They develop earliest signs at about 15 days of age, similar to la, are runted but fertile and can live for months. Clinical signs are ataixa, stiffness, retarded motor activity and intermittent focal seizures. The pathological basis for these symptoms is still elusive. The three types of mice, la/la, la/tg and tgjtg are thus distinct clinically, la/tg resembling in some respect either of the other two.
INTRODUCTIONTottering (gene symbol, tg) and leaner (la) are autosomal recessive mutations of the mouse. Both cause neuromuscular disorders but their clinical and pathological characteristics are different. Tottering is classified with a group of other mutations characterized by epileptiform seizures, and leaner is a so-called cerebellar mutant because of severe pathological lesions involving mainly the cerebellen (see Sidman, Green & Appel, 1965). The tg locus is in linkage group XVIII in close proximity to .Es-1, a locus controlling esterase-1 isozymes (Green, 1966). The linkage group of la, prior to this study, has not been known.In the course of studies on the genetic control of non-specific esterase isozymes in neuromuscular mutants we determined the Es-1 phenotypes of tgjtg and la /la mice. As a consequence of these studies we were interested in the possible genetic relationship of the two mutant types. Our findings indicate that la and tg are allelic. This paper presents the results of our breeding tests and isozyme determinations. Further, it describes the clinical and preliminary pathological findings in lajtg mice.
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