Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: a potential animal model for schizophrenia and autism.
Schizophrenia and autism are neurodevelopmental disorders with genetic and environmental etiologies. Prenatal viral infection has been associated with both disorders. We investigated the effects of prenatal viral infection on gene regulation in offspring of Balb-c mice using microarray technology. The results showed significant upregulation of 21 genes and downregulation of 18 genes in the affected neonatal brain homogenates spanning gene families affecting cell structure and function, namely, cytosolic chaperone system, HSC70, Bicaudal D, aquaporin 4, carbonic anhydrase 3, glycine receptor, norepinephrine transporter, and myelin basic protein. We also verified the results using QPCR measurements of selected mRNA species. These results show for the first time that prenatal human influenza viral infection on day 9 of pregnancy leads to alterations in a subset of genes in brains of exposed offspring, potentially leading to permanent changes in brain structure and function.
Fatemi
S H
SH
University of Minnesota, Department of Psychiatry, Division of Neuroscience Research, Minneapolis, Minnesota 55455, USA. fatem002@umn.edu
Pearce
D A
DA
Brooks
A I
AI
Sidwell
R W
RW
D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000821:virology*; D020805:Central Nervous System Viral Diseases / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009976:Orthomyxoviridae Infections / Q000150:complications; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000821:virology*; D015854:Up-Regulation / Q000235:genetics
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger