Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice

K. Y. Ryu, N. Fujiki, M. Kazantzis, J. C. Garza, D. M. Bouley, A. Stahl, Xinyun Lu, S. Nishino, R. R. Kopito

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aims: Ubiquitin performs essential roles in a myriad of signalling pathways required for cellular function and survival. Recently, we reported that disruption of the stress-inducible ubiquitin-encoding gene Ubb reduces ubiquitin content in the hypothalamus and leads to adult-onset obesity coupled with a loss of arcuate nucleus neurones and disrupted energy homeostasis in mice. Neuropeptides expressed in the hypothalamus control both metabolic and sleep behaviours. In order to demonstrate that the loss of Ubb results in broad hypothalamic abnormalities, we attempted to determine whether metabolic and sleep behaviours were altered in Ubb knockout mice. Methods: Metabolic rate and energy expenditure were measured in a metabolic chamber, and sleep stage was monitored via electroencephalographic/electromyographic recording. The presence of neurodegeneration and increased reactive gliosis in the hypothalamus were also evaluated. Results: We found that Ubb disruption leads to early-onset reduced activity and metabolic rate. Additionally, we have demonstrated that sleep behaviour is altered and sleep homeostasis is disrupted in Ubb knockout mice. These early metabolic and sleep abnormalities are accompanied by persistent reactive gliosis and the loss of arcuate nucleus neurones, but are independent of neurodegeneration in the lateral hypothalamus. Conclusions:Ubb knockout mice exhibit phenotypes consistent with hypothalamic dysfunction. Our data also indicate that Ubb is essential for the maintenance of the ubiquitin levels required for proper regulation of metabolic and sleep behaviours in mice.

Original languageEnglish (US)
Pages (from-to)285-299
Number of pages15
JournalNeuropathology and Applied Neurobiology
Volume36
Issue number4
DOIs
StatePublished - Jan 1 2010

Fingerprint

Polyubiquitin
Sleep
Ubiquitin
Knockout Mice
Genes
Hypothalamus
Arcuate Nucleus of Hypothalamus
Gliosis
Homeostasis
Lateral Hypothalamic Area
Neurons
Sleep Stages
Neuropeptides
Energy Metabolism
Obesity
Maintenance
Phenotype

Keywords

  • Glial fibrillary acidic protein
  • Hypothalamus
  • Knockout mice
  • Metabolism
  • Polyubiquitin gene
  • Sleep

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Ryu, K. Y., Fujiki, N., Kazantzis, M., Garza, J. C., Bouley, D. M., Stahl, A., ... Kopito, R. R. (2010). Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice. Neuropathology and Applied Neurobiology, 36(4), 285-299. https://doi.org/10.1111/j.1365-2990.2009.01057.x

Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice. / Ryu, K. Y.; Fujiki, N.; Kazantzis, M.; Garza, J. C.; Bouley, D. M.; Stahl, A.; Lu, Xinyun; Nishino, S.; Kopito, R. R.

In: Neuropathology and Applied Neurobiology, Vol. 36, No. 4, 01.01.2010, p. 285-299.

Research output: Contribution to journalArticle

Ryu, KY, Fujiki, N, Kazantzis, M, Garza, JC, Bouley, DM, Stahl, A, Lu, X, Nishino, S & Kopito, RR 2010, 'Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice', Neuropathology and Applied Neurobiology, vol. 36, no. 4, pp. 285-299. https://doi.org/10.1111/j.1365-2990.2009.01057.x
Ryu, K. Y. ; Fujiki, N. ; Kazantzis, M. ; Garza, J. C. ; Bouley, D. M. ; Stahl, A. ; Lu, Xinyun ; Nishino, S. ; Kopito, R. R. / Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice. In: Neuropathology and Applied Neurobiology. 2010 ; Vol. 36, No. 4. pp. 285-299.
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