Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the collapsin response mediator protein (CRMP) family are reported to be involved in the pathogenesis of various neuronal disorders, including schizophrenia and autism. One of them, CRMP4, is reported to participate in aspects of neuronal development, such as axonal guidance and dendritic development. However, no physiological or behavioral phenotypes in Crmp4 knockout (Crmp4-KO) mice have been identified, making it difficult to elucidate the in vivo roles of CRMP4. Focusing on the olfaction process because of the previous study showing strong expression of Crmp4 mRNA in the olfactory bulb (OB) during the early postnatal period, it was aimed to test the hypothesis that Crmp4-KO pups would exhibit abnormal olfaction. Based on measurements of their ultrasonic vocalizations, impaired olfactory ability in Crmp4-KO pups was found. In addition, c-Fos expression, a marker of neuron activity, revealed hyperactivity in the OB of Crmp4-KO pups compared with wild-types following exposure to an odorant. Moreover, the mRNA and protein expression levels of glutamate receptor 1 (GluR1) and 2 (GluR2) were exaggerated in Crmp4-KO pups relative to other excitatory and inhibitory receptors and transporters, raising the possibility that enhanced expression of these excitatory receptors contributes to the hyperactivity phenotype and impairs olfactory ability. This study provides evidence for an animal model for elucidating the roles of CRMP4 in the development of higher brain functions as well as for elucidating the developmental regulatory mechanisms controlling the activity of the neural circuitry.
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PMID:Mouse pups lacking collapsin response mediator protein 4 manifest impaired olfactory function and hyperactivity in the olfactory bulb. 2611 40

Autism spectrum disorders (ASD) are more common among boys than girls. The mechanisms responsible for ASD symptoms and their sex differences remain mostly unclear. We previously identified collapsin response mediator protein 4 (CRMP4) as a protein exhibiting sex-different expression during sexual differentiation of the hypothalamic sexually dimorphic nucleus. This study investigated the relationship between the sex-different development of autistic features and CRMP4 deficiency. Whole-exome sequencing detected a de novo variant (S541Y) of CRMP4 in a male ASD patient. The expression of mutated mouse CRMP4 S540Y, which is homologous to human CRMP4 S541Y, in cultured hippocampal neurons derived from Crmp4-knockout (KO) mice had increased dendritic branching, compared to those transfected with wild-type (WT) Crmp4, indicating that this mutation results in altered CRMP4 function in neurons. Crmp4-KO mice showed decreased social interaction and several alterations of sensory responses. Most of these changes were more severe in male Crmp4-KO mice than in females. The mRNA expression levels of some genes related to neurotransmission and cell adhesion were altered in the brain of Crmp4-KO mice, mostly in a gender-dependent manner. These results indicate a functional link between a case-specific, rare variant of one gene, Crmp4, and several characteristics of ASD, including sexual differences.
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PMID:Human CRMP4 mutation and disrupted Crmp4 expression in mice are associated with ASD characteristics and sexual dimorphism. 2919 32

Previous research has demonstrated that the collapsin response mediator protein (CRMP) family is involved in the formation of neural networks. A recent whole-exome sequencing study identified a de novo variant (S541Y) of collapsin response mediator protein 4 (CRMP4) in a male patient with autism spectrum disorder (ASD). In addition, Crmp4-knockout (KO) mice show some phenotypes similar to those observed in human patients with ASD. For example, compared with wild-type mice, Crmp4-KO mice exhibit impaired social interaction, abnormal sensory sensitivities, broader distribution of activated (c-Fos expressing) neurons, altered dendritic formation, and aberrant patterns of neural gene expressions, most of which have sex differences. This review summarizes current knowledge regarding the role of CRMP4 during brain development and discusses the possible contribution of CRMP4 deficiencies or abnormalities to the pathogenesis of ASD. Crmp4-KO mice represent an appropriate animal model for investigating the mechanisms underlying some ASD phenotypes, such as impaired social behavior, abnormal sensory sensitivities, and sex-based differences, and other neurodevelopmental disorders associated with sensory processing disorders.
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PMID:Crmp4-KO Mice as an Animal Model for Investigating Certain Phenotypes of Autism Spectrum Disorders. 3113 94