TY - JOUR
T1 - Animals lacking endothelin-converting enzyme-2 are deficient in learning and memory
AU - Rodriguiz, R. M.
AU - Gadnidze, K.
AU - Ragnauth, A.
AU - Dorr, N.
AU - Yanagisawa, M.
AU - Wetsel, W. C.
AU - Devi, L. A.
PY - 2008/6
Y1 - 2008/6
N2 - Endothelin-converting enzyme (ECE)-2 is a metalloprotease that possesses many properties consistent with it being a neuropeptide-processing enzyme. This protease is found primarily in neural tissues, with high levels of expression in midbrain, cerebellum, hypothalamus, frontal cortex and spinal cord and moderate levels in hippocampus and striatum. To evaluate its role in neural function, mice have been generated lacking this enzyme. Physical appearance, autonomic reflexes, motor co-ordination, balance, locomotor activity and spontaneous emotional responses appear normal in these knockout (KO) mice. However, these mutants display deficits in learning and memory as evidenced by marked impairment in the Morris water maze. Knockout mice are also deficient in object recognition memory where they show delays in discerning changes in object location and in recognizing the introduction of a novel object. In this study, perseveration appears to interfere with learning and memory. Finally, mutants are impaired in social transmission of food preference where they show poor short-term memory and perturbations in long-term memory; the latter can be ameliorated by reminder cues. As ECE-2 has been implicated in Alzheimer's disease, the deficits in learning and memory in the KO mice may provide unique insights into processes that may contribute to this disease and possible other disorders of cognition.
AB - Endothelin-converting enzyme (ECE)-2 is a metalloprotease that possesses many properties consistent with it being a neuropeptide-processing enzyme. This protease is found primarily in neural tissues, with high levels of expression in midbrain, cerebellum, hypothalamus, frontal cortex and spinal cord and moderate levels in hippocampus and striatum. To evaluate its role in neural function, mice have been generated lacking this enzyme. Physical appearance, autonomic reflexes, motor co-ordination, balance, locomotor activity and spontaneous emotional responses appear normal in these knockout (KO) mice. However, these mutants display deficits in learning and memory as evidenced by marked impairment in the Morris water maze. Knockout mice are also deficient in object recognition memory where they show delays in discerning changes in object location and in recognizing the introduction of a novel object. In this study, perseveration appears to interfere with learning and memory. Finally, mutants are impaired in social transmission of food preference where they show poor short-term memory and perturbations in long-term memory; the latter can be ameliorated by reminder cues. As ECE-2 has been implicated in Alzheimer's disease, the deficits in learning and memory in the KO mice may provide unique insights into processes that may contribute to this disease and possible other disorders of cognition.
KW - Hippocampus
KW - Learning
KW - Memory
KW - Metalloendoproteases
KW - Mutant mice
KW - Neuropeptide biosynthesis
KW - Posttranslational processing
UR - http://www.scopus.com/inward/record.url?scp=42549111585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42549111585&partnerID=8YFLogxK
U2 - 10.1111/j.1601-183X.2007.00365.x
DO - 10.1111/j.1601-183X.2007.00365.x
M3 - Article
C2 - 21450041
AN - SCOPUS:42549111585
SN - 1601-1848
VL - 7
SP - 418
EP - 426
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
IS - 4
ER -