Fmr-1 as an offspring genetic and a maternal environmental factor in neurodevelopmental disease.
Since fragile X syndrome (FXS) is a typical X-linked mendelian disorder, the protein product associated with the disease (FMRP) is absent or reduced not only in the affected individuals but, in case of full mutation, also in their mothers. Here, by using the mouse model of the disease, we provide evidence that hyperactivity, a typical symptom of FXS, is not wholly induced by the lack of Fmrp in mice but also occurs as a result of its reduced expression in their mother. Genetically wild-type offspring of mutant mothers also had hyperactivity, albeit less pronounced than the mutant offspring. However, other features of FXS reproduced in the mouse model, such as sensory hyperreactivity and seizure susceptibility, were exclusively associated with the absence of Fmrp in the offspring. These data indicate that fmr-1, the gene encoding Fmrp, can be both an offspring genetic and a maternal environmental factor in producing a neurodevelopmental condition.
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA. boz2001@med.cornell.edu
Bojana
B
Zupan
Miklos
M
Toth
D000818:Animals; D001519:Behavior / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004777:Environment; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000473:pathology / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D018811:Maternal Exposure; D051379:Mice; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology
D004298:Dopamine; D051860:Fragile X Messenger Ribonucleoprotein 1