title: Phenotypic changes in calbindin D28K immunoreactivity in the hippocampus of Fmr1 knockout mice.
abstract: Fragile X syndrome (FXS), the most prevalent form of inherited mental retardation, is caused by the lack of FMRP (fragile mental retardation protein) as a result of the transcriptional silencing of the FMR1 gene. Here we analyze the immunohistochemical expression of the calbindin D28K protein in the hippocampus of Fmr1 knockout (KO) mice and compare it with that of their wildtype (WT) littermates. The spatial distribution pattern of calbindin-immunoreactive cells in the hippocampus was similar in WT and KO mice but for each age studied (ranging from 3.5-8 months) the dentate gyrus of Fmr1-KO mice showed a significant reduction in calbindin-immunoreactive granule cells. Also, the number of calbindin-immunoreactive cells was reduced in the CA1 pyramidal layer in KO mice compared to their WT littermates. In addition, Frm1-KO mice showed a group of calbindin-immunoreactive cells located only in the left CA3b subregion that was only sometimes observed in WT mice. Overall, the absence of FMRP results in a dysregulation of the calbindin protein expression in the hippocampus. This dysregulation is cell type- and time-dependent and as a consequence key elements of the hippocampal trisynaptic circuitry may lack calbindin in critical periods for normal memory/learning abilities to be achieved and may explain some of the FXS symptoms observed in the Fmr1-KO mouse model.
authors.affiliation: University of Málaga, Department of Cell Biology, Genetics, and Physiology, Málaga, Spain.
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Real
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Simón
authors.forename: Raúl
authors.initials: R
authors.lastname: Heredia
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Diego
authors.forename: Salvador
authors.initials: S
authors.lastname: Guirado
mesh_terms: D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D064092:Calbindin 1; D064026:Calbindins; D051860:Fragile X Messenger Ribonucleoprotein 1; D018698:Glutamic Acid; D064030:S100 Calcium Binding Protein G; C576498:CALB1 protein, human; C576499:Calb1 protein, mouse; C497684:Fmr1 protein, mouse