SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice
| Autor: | Nicola M. Solomon, Shengwen Zhang, Uta Francke, Feng Ding, Sally A. Camper, Hong Hua Li, Pinchas Cohen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Neurological Disorders/Developmental and Pediatric Neurology Chromosomal translocation Energy homeostasis Diabetes and Endocrinology/Obesity Immunoenzyme Techniques Mice Nutrition/Obesity Insulin-Like Growth Factor I Growth Disorders Multidisciplinary Neuroscience/Behavioral Neuroscience Behavior Animal Reverse Transcriptase Polymerase Chain Reaction Neuroscience/Neurodevelopment Hypotonia Ghrelin Blotting Southern Medicine Female medicine.symptom Prader-Willi Syndrome Research Article medicine.medical_specialty Somatotropic cell Science Enzyme-Linked Immunosorbent Assay Biology Hyperphagia Short stature Oxygen Consumption Internal medicine Genetics and Genomics/Epigenetics medicine Animals RNA Small Nucleolar RNA Messenger Molecular Biology Integrases Pediatrics and Child Health/Child Development Abnormal Growth Hormone Mice Inbred C57BL Disease Models Animal Endocrinology Genetics and Genomics/Disease Models Nutrition/Eating Disorders Animals Newborn Genomic imprinting Energy Metabolism Gene Deletion |
| Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 3, p e1709 (2008) |
| ISSN: | 1932-6203 |
| Popis: | Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation. |
| Databáze: | OpenAIRE |
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