Neonatal maternal deprivation response and developmental changes in gene expression revealed by hypothalamic gene expression profiling in mice.
Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.
Ding
Feng
F
Department of Genetics, Stanford University, Stanford, California, United States of America.
Li
Hong Hua
HH
Li
Jun
J
Myers
Richard M
RM
Francke
Uta
U
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D005508:Food Deprivation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011218:Prader-Willi Syndrome / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020537:RNA, Small Nucleolar