ArticlePloS one2015
Metabolic and Behavioural Phenotypes in Nestin-Cre Mice Are Caused by Hypothalamic Expression of Human Growth Hormone.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Article
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- Absence of Ledgf in mouse brain affects the Kmt2a/b and polycomb balance, synaptic transmission and motor function.Acta neuropathologica communications · 2026Article
- Growth Hormone and IGF-1 Actions in the Brain and Neuropsychiatric Diseases.Physiology (Bethesda, Md.) · 2026Review
- Systemic Glucose Homeostasis Requires Pancreatic but Not Neuronal ATP-sensitive Potassium Channels.Function (Oxford, England) · 2025Article
- Functional connectivity changes in mouse models of maple syrup urine disease.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Growth Hormone Receptor in Lateral Hypothalamic Neurons Is Required for Increased Food-Seeking Behavior during Food Restriction in Male Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury.Journal of neuroinflammation · 2024Article
- CLUH maintains functional mitochondria and translation in motoneuronal axons and prevents peripheral neuropathy.Science advances · 2024Article
- NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis.Molecular psychiatry · 2024Article
- Crucial role of TFAP2B in the nervous system for regulating NREM sleep.Molecular brain · 2024Article
- Effects of Bradykinin B2 Receptor Ablation from Tyrosine Hydroxylase Cells on Behavioral and Motor Aspects in Male and Female Mice.International journal of molecular sciences · 2024Article
- Modifications of the GH Axis Reveal Unique Sexually Dimorphic Liver Signatures forJournal of the Endocrine Society · 2024Article
- Sex-specific effects of alcohol on neurobehavioral performance and endoplasmic reticulum stress: an analysis using neuron-specific MANF deficient mice.Frontiers in pharmacology · 2024Article
- Serine Racemase mediates subventricular zone neurogenesis via fatty acid metabolism.Stem cell reports · 2023Article
- Sex-specific effects of Cre expression in Syn1Cre mice.Scientific reports · 2023Article
- Central growth hormone action regulates neuroglial and proinflammatory markers in the hypothalamus of male mice.Neuroscience letters · 2023Article
- Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Sex linked behavioral and hippocampal transcriptomic changes in mice with cell-type specificFrontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Nestin-Cre driver mouse line has mild hypopituitarism, reduced body weight, a metabolic phenotype and reduced anxiety. Although several causes have been suggested, a comprehensive explanation is still lacking. In this study we examined the molecular mechanisms leading to this compound phenotype. Upon generation of the Nestin-Cre mice, the human growth hormone (hGH) minigene was inserted downstream of the Cre recombinase to ensure efficient transgene expression. As a result, hGH is expressed in the hypothalamus. This results in the auto/paracrine activation of the GH receptor as demonstrated by the increased phosphorylation of signal transducer and activator of transcription 5 (STAT5) and reduced expression of growth hormone releasing hormone (Ghrh). Low Ghrh levels cause hypopituitarism consistent with the observed mouse growth hormone (mGH) deficiency. mGH deficiency caused reduced activation of the GH receptor and hence reduced phosphorylation of STAT5 in the liver. This led to decreased levels of hepatic Igf-1 mRNA and consequently postnatal growth retardation. Furthermore, genes involved in lipid uptake and synthesis, such as CD36 and very low-density lipoprotein receptor were upregulated, resulting in liver steatosis. In conclusion, this study demonstrates the unexpected expression of hGH in the hypothalamus of Nestin-Cre mice which is able to activate both the GH receptor and the prolactin receptor. Increased hypothalamic GH receptor signaling explains the observed hypopituitarism, reduced growth and metabolic phenotype of Nestin-Cre mice. Activation of either receptor is consistent with reduced anxiety.
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