No abstract

The 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

15q13.3 microdeletion syndrome is a genetic disorder caused by a deletion of a region containing seven genes on chromosome 15, MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7, and characterized by a wide spectrum of psychiatric disorders. The contribution of each gene in this syndrome has been studied using mutant mouse models, but the phenotypes of these mice do not account for human phenotypes and the results are still controversial. The behavior of Trpm1−/− mice with relation to 15q13.3 microdeletion syndrome has not been investigated due to the visual impairment in these mice, which may confound the results of behavior tests that involve vision. We have now applied a comprehensive behavioral test battery to examine the relationship of TRPM1 and 15q13.3 microdeletion syndrome by using Trpm1 null mutant mice. Our data indicate abnormal behavior of Trpm1−/− mice which may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduction of anxiety behavior, abnormality of social interaction, attenuation in fear memory, and hyperactivity, which is the most prominent phenotype of Trpm1 mutant mice. While the ON visual transduction pathway is impared in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. Although Trpm1−/− mice share the same pathway for visual impairment with mGluR6−/− mice, hyperlocomotion activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. This is the first evidence to associate TRPM1 with impairment of cognitive function similar to that found in the phenotypes of 15q13.3 microdeletion syndrome.

15q13.3 microdeletion syndrome is a genetic disorder caused by a deletion of a region containing seven genes on chromosome 15, MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7, and characterized by a wide spectrum of psychiatric disorders. The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice with relation to 15q13.3 microdeletion syndrome has not been investigated due to the visual impairment in these mice, which may confound the results of behavioral tests that involve vision. We have now performed a comprehensive behavioral test battery in Trpm1 null mutant mice to demonstrate the role of Trpm1, which is thought to be solely expressed in the retina, in central nervous system and to examine the relationship of TRPM1 and 15q13.3 microdeletion syndrome. Our data indicate abnormal behavior of Trpm1−/− mice which may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduction of anxiety-like behavior, abnormality of social interaction, attenuation in fear memory, and hyperactivity, which is the most prominent phenotype of Trpm1 mutant mice. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. Although Trpm1−/− mice share the same pathway for visual impairment with mGluR6-/- mice, hyperlocomotor activity has not been reported in mGluR6-/- mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. This is the first evidence to associate TRPM1 with impairment of cognitive function similar to that found in the phenotypes of 15q13.3 microdeletion syndrome.