title: LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease.
abstract: Several psychiatric diseases, including schizophrenia, are thought to have a developmental aetiology, but to date no clear link has been made between psychiatric disease and a specific developmental process. LPA(1) is a G(i)-coupled seven transmembrane receptor with high affinity for lysophosphatidic acid. Although LPA(1) is expressed in several peripheral tissues, in the nervous system it shows relatively restricted temporal expression to neuroepithelia during CNS development and to myelinating glia in the adult. We report the detailed neurological and behavioural analysis of mice homozygous for a targeted deletion at the lpa(1) locus. Our observations reveal a marked deficit in prepulse inhibition, widespread changes in the levels and turnover of the neurotransmitter 5-HT, a brain region-specific alteration in levels of amino acids, and a craniofacial dysmorphism in these mice. We suggest that the loss of LPA(1) receptor generates defects resembling those found in psychiatric disease.
authors.affiliation: Comparative Genomics, GlaxoSmithKline, Harlow, Essex, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Harrison
authors.forename: C
authors.initials: C
authors.lastname: Reavill
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.forename: J T
authors.initials: JT
authors.lastname: Brown
authors.forename: J E
authors.initials: JE
authors.lastname: Cluderay
authors.forename: B
authors.initials: B
authors.lastname: Crook
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: L A
authors.initials: LA
authors.lastname: Dawson
authors.forename: E
authors.initials: E
authors.lastname: Grau
authors.forename: C
authors.initials: C
authors.lastname: Heidbreder
authors.forename: P
authors.initials: P
authors.lastname: Hemmati
authors.forename: G
authors.initials: G
authors.lastname: Hervieu
authors.forename: A
authors.initials: A
authors.lastname: Howarth
authors.forename: Z A
authors.initials: ZA
authors.lastname: Hughes
authors.forename: A J
authors.initials: AJ
authors.lastname: Hunter
authors.forename: J
authors.initials: J
authors.lastname: Latcham
authors.forename: S
authors.initials: S
authors.lastname: Pickering
authors.forename: P
authors.initials: P
authors.lastname: Pugh
authors.forename: D C
authors.initials: DC
authors.lastname: Rogers
authors.forename: C S
authors.initials: CS
authors.lastname: Shilliam
authors.forename: P R
authors.initials: PR
authors.lastname: Maycox
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011930:Reaction Time / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid; D013216:Reflex, Startle / Q000502:physiology
chemical_list: D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid