scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 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.

scholarly journals Mice with mutations in Trpm1, a gene within the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.

2021 ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Abnormal Behavior ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
Null Mutant Mice ◽  
Relationship Of

Abstract 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.

scholarly journals Mice with Mutations in Trpm1, a Gene within the locus of 15q13.3 Microdeletion Syndrome, Display Pronounced Hyperactivity and Decreased Anxiety-Like Behavior.

2020 ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Abnormal Behavior ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
Null Mutant Mice ◽  
Relationship Of

Abstract 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.

scholarly journals Role of RANKL (TNFSF11)-Dependent Osteopetrosis in the Dental Phenotype of Msx2 Null Mutant Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80054 ◽  
Author(s):  
Beatriz Castaneda ◽  
Yohann Simon ◽  
Didier Ferbus ◽  
Benoit Robert ◽  
Julie Chesneau ◽  
...  
Keyword(s):  
Mutant Mice ◽  
Null Mutant ◽  
Null Mutant Mice

scholarly journals Role of nNOS in Blood Pressure Regulation in eNOS Null Mutant Mice

Hypertension ◽  
1998 ◽  
Vol 32 (5) ◽  
pp. 856-861 ◽  
Author(s):  
Nobutaka Kurihara ◽  
Marcos E. Alfie ◽  
David H. Sigmon ◽  
Nour-Eddine Rhaleb ◽  
Edward G. Shesely ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Regulation ◽  
Mutant Mice ◽  
Pressure Regulation ◽  
Null Mutant ◽  
Null Mutant Mice

scholarly journals Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability

2020 ◽  
Vol 6 (8) ◽  
pp. eaax4568 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Filipe Nascimento ◽  
Rafael Luján ◽  
Ana P. Luiz ◽  
Queensta Millet ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Dorsal Horn Neuron ◽  
Mutant Mice ◽  
Afferent Neuron ◽  
Null Mutant ◽  
Dorsal Horn Neurons ◽  
Afferent Nerves ◽  
Horn Neuron ◽  
Null Mutant Mice

Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

scholarly journals Mycobacterium abscessuscording prevents phagocytosis and promotes abscess formation

2014 ◽  
Vol 111 (10) ◽  
pp. E943-E952 ◽  
Author(s):  
Audrey Bernut ◽  
Jean-Louis Herrmann ◽  
Karima Kissa ◽  
Jean-François Dubremetz ◽  
Jean-Louis Gaillard ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Wide Spectrum ◽  
Mycobacterium Abscessus ◽  
Abscess Formation ◽  
Zebrafish Embryos ◽  
Clinical Syndromes ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Mycobacterium abscessusis a rapidly growingMycobacteriumcausing a wide spectrum of clinical syndromes. It now is recognized as a pulmonary pathogen to which cystic fibrosis patients have a particular susceptibility. TheM. abscessusrough (R) variant, devoid of cell-surface glycopeptidolipids (GPLs), causes more severe clinical disease than the smooth (S) variant, but the underlying mechanisms of R-variant virulence remain obscure. Exploiting the optical transparency of zebrafish embryos, we observed that the increased virulence of theM. abscessusR variant compared with the S variant correlated with the loss of GPL production. The virulence of the R variant involved the massive production of serpentine cords, absent during S-variant infection, and the cords initiated abscess formation leading to rapid larval death. Cording occurred within the vasculature and was highly pronounced in the central nervous system (CNS). It appears thatM. abscessusis transported to the CNS within macrophages. The release ofM. abscessusfrom apoptotic macrophages initiated the formation of cords that grew too large to be phagocytized by macrophages or neutrophils. This study is a description of the crucial role of cording in the in vivo physiopathology ofM. abscessusinfection and emphasizes cording as a mechanism of immune evasion.

scholarly journals The Role of Genetics Mutation in Gene Tgm5 in Induce Acral Peeling Skin Syndrome

2019 ◽  
Vol 4 (3) ◽  
Keyword(s):  
Genetic Disorder ◽  
Skin Lesions ◽  
Chromosome 15

APS syndrome is a skin-related genetic disorder characterized by painless skin lesions from the upper layer of the skin. In addition to the above, sometimes peeling of the skin in the arms and legs also occurs. Skin peeling usually appears at birth, but can begin in childhood or later in life. APS syndrome is caused by the mutation of the TGM5 gene, which is based on the long arm of chromosome 15 as 15q15.2.

scholarly journals New Insights Into the Role of Aberrant Hippocampal Neurogenesis in Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Chen ◽  
Fuchao Chen ◽  
Yue Wu ◽  
Benhong Zhou
Keyword(s):  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Future Directions ◽  
The Past ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
Patients With Epilepsy

Data accumulated over the past four decades have confirmed that adult hippocampal neurogenesis (HN) plays a key role in the wide spectrum of hippocampal pathology. Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although neurogenesis in persistent germinative zones is altered in the adult rodent models of epilepsy, the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. In this review, we described the most recent advances in neurogenesis in epilepsy and outlooked future directions for neural stem cells (NSCs) and epilepsy-in-a-dish models. We proposed that it may help in refining the underlying molecular mechanisms of epilepsy and improving the therapies and precision medicine for patients with epilepsy.

scholarly journals Dissociation of Locomotor Activation and Suppression of Food Intake Induced by CRF in CRFR1-Deficient Mice

Endocrinology ◽  
2000 ◽  
Vol 141 (7) ◽  
pp. 2698-2702 ◽  
Author(s):  
Angelo Contarino ◽  
Françoise Dellu ◽  
George F. Koob ◽  
George W. Smith ◽  
Kuofen Lee ◽  
...  
Keyword(s):  
Corticotropin Releasing Factor ◽  
Mutant Mice ◽  
Receptor Subtypes ◽  
Null Mutant ◽  
Wild Type ◽  
Feeding Behaviors ◽  
The Central Nervous System ◽  
Locomotor Activation ◽  
Null Mutant Mice ◽  
Deficient Mice

ABSTRACT Corticotropin-releasing factor (CRF) systems are involved in locomotor and feeding behaviors. Two distinct CRF receptor subtypes, CRFR1 and CRFR2, are thought to mediate CRF actions in the central nervous system. However, the role for each receptor in locomotor activity and feeding remains to be determined. Using CRFR1 null mutant mice, the present study examined the functional significance of this receptor in ambulation and feeding. CRF treatment of wild-type mice resulted in increased levels of locomotion whereas no change was observed in CRFR1-deficient mice as compared to vehicle-treated mutant mice. In contrast, CRF decreased food-water intake in both wild type and CRFR1-deficient mice equally. These results support an important role for CRFR1 in mediating CRF-induced locomotor activation, whereas other receptor subtypes, likely CRFR2, may mediate the appetite-suppressing effects of CRF-like peptides.

Targeted Inactivation of the Mouse Locus Encoding Coagulation Factor XIII-A: Hemostatic Abnormalities in Mutant Mice and Characterization of the Coagulation Deficit

2002 ◽  
Vol 88 (12) ◽  
pp. 967-974 ◽  
Author(s):  
Peter Lauer ◽  
Hubert Metzner ◽  
Gerd Zettlmeißl ◽  
Meng Li ◽  
Austin Smith ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Factor Xiii ◽  
Genetic Disorder ◽  
Coagulation Factor ◽  
Mutant Mice ◽  
Targeted Deletion ◽  
Coagulation Factor Xiii ◽  
Tail Tip ◽  
Human Genetic Disorder

SummaryBlood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin γ-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin® P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

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