Short communicationImpairment of sensorimotor gating in mice deficient in the cell adhesion molecule L1 or its close homologue, CHL1
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Acknowledgements
The authors are grateful to Peggy Putthoff for genotyping. The studies were supported in part by grants from the NIH to P.M. (NS26620 and MH064056) and a NARSAD Young Investigator Award to L.K.N.
References (18)
- et al.
Role of L1 in neural development: what the knockouts tell us
Mol. Cell. Neurosci.
(1998) - et al.
Genome scan meta-analysis of schizophrenia and bipolar disorder: Part II. Schizophrenia
Am. J. Hum. Genet.
(2003) - et al.
Mice deficient for the close homologue of the neural adhesion cell L1 (CHL1) display alterations in emotional reactivity and motor coordination
Behav. Brain Res.
(2003) - et al.
Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in juvenile mice deficient in the neural cell adhesion molecule L1
Mol. Cell. Neurosci.
(2004) - et al.
Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies
Psychopharmacology (Berl)
(2001) - et al.
Disruption of the mouse L1 gene leads to malformations of the nervous system
Nat. Genet.
(1997) - et al.
Abnormalities in neuronal process extension, hippocampal development, and the ventricular system of L1 knockout mice
J. Neurosci.
(1999) - et al.
Close homolog of L1 (CHL1) modulates area-specific neuronal migration and dendrite orientation in the cerebral cortex
Neuron
(2004) - et al.
A new role for the cell adhesion molecule L1 in neural precursor cell proliferation, differentiation, and transmitter-specific subtype generation
J. Neurosci.
(2003)
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Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia
2017, Behavioural Brain ResearchCitation Excerpt :CHL1 and other cell adhesion molecules of the immunoglobulin superfamily are highly expressed during the development of the nervous system [13], have multiple functions in the formation of appropriate neuronal connections during development [14] and in synaptic function and plasticity in the adult [15], processes which are thought to be disrupted in intellectual disabilities and schizophrenia [16]. CHL1-deficient mice [17] exhibit behavioral alterations suggestive of those found in schizophrenic patients [18–23], such as impaired sensorimotor gating (prepulse inhibition) [24,25] and reduced exploratory behavior in novel environments [17,26]. Timekeeping is disrupted in schizophrenic patients and individuals at risk for schizophrenia [22,27–31], as well as CHL1-deficient mice [32].
Increased temporal discounting after chronic stress in CHL1-deficient mice is reversed by 5-HT2C agonist Ro 60-0175
2017, NeuroscienceCitation Excerpt :Genetic associations between CHL1 gene polymorphisms and schizophrenia (Sakurai et al., 2002; Chen et al., 2005; Shaltout et al., 2013) were found in Asian populations and rare copy number variants of this gene were identified in a Scottish study (Tam et al., 2010). Prepulse inhibition of the acoustic startle response is impaired in CHL1-KO mice, which can thus model sensorimotor gating impairments found in schizophrenic patients (Irintchev et al., 2004). Our current results show that other SZ-like deficits, such as impulsivity, can be revealed in these mice by stress, supporting a ‘double hit’ hypothesis (Bayer et al., 1999).
Heterozygous deletion of CHL1 gene: Detailed array-CGH and clinical characterization of a new case and review of the literature
2014, European Journal of Medical GeneticsCitation Excerpt :The importance of CHL1 function is pointed out by studies in partially or completely Chl1deficient mice, showing defects in neurotransmission, behavior, motor coordination, fiber organization in both olfactory bulb and hippocampus, and migration of cortical neurons. Moreover, a gene dosage effect of CHL1 expression levels was demonstrated [Frints et al., 2003; Demyanenko et al., 2004; Irintchev et al., 2004; Pratte and Jamon, 2004]. In humans, heterozygous loss of CHL1 gene has been associated with cognitive impairment characterized by learning and language difficulties.
Loss of function studies in mice and genetic association link receptor protein tyrosine phosphatase α to schizophrenia
2011, Biological PsychiatryCitation Excerpt :Absence of the NCAM isoform NCAM180 leads to increased lateral ventricle size, one of the most reliable morphological features in brains of schizophrenics, and is often accompanied by cognitive impairments (70). Association studies implicate NCAM and CHL1 in human SZ risk, and LOF of the corresponding genes in mice engenders intriguing phenotypic overlaps with Ptpra LOF in terms of cortical radial migration (72), dendrite orientation (24), impaired long-term potentiation (69), and impaired sensorimotor gating/PPI (73). Thus, phenotypes observed in Ptpra−/− mice could be mediated by the effect of RPTPα on these molecules.
Impairment of novelty detection in mice targeted for the Chl1 gene
2009, Physiology and BehaviorModulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules
2008, Neuron Glia Biology