Sci. Aging Knowl. Environ., 15 June 2005
Vol. 2005, Issue 24, p. tg4
GENETICALLY ALTERED MICE
CB1 Knockout Mice
||See Pryce et al. (2003).
||Cannabinoid Receptor 1 (CB1; CNR1)
|Type of change
||Targeted disruption of the gene.
|Nature of protein
||The CB1 locus encodes an integral membrane-bound GTP-binding protein-coupled receptor (GPCR) possessing seven transmembrane domains and belonging to the rhodopsin-like superfamily of GPCR proteins.
||CB1 knockout mice display increased bone mineral density as compared with normal littermates. CB1 knockouts are also completely resistant to trabecular bone loss induced by ovariectomy, suggesting an important role for this receptor in hormonal regulation of bone loss.
The CB1-selective antagonist AM251 was shown to inhibit the formation of osteoclasts (cells responsible for the breakdown of bone; see "The Plot Thickens on Thin Bones"), whereas cultured osteoclast cells derived from CB1 knockout mice are resistant to the effects of AM251.
|Corresponding human phenotype
||Unknown; the human homolog cannabinoid receptor 1 (CNR1) has been mapped to chromosome 6q14-q15.
||A. I. Idris, R. J. van 't Hof, I. R. Greig, S. A. Ridge, D. Baker, R. A. Ross, S. H. Ralston, Regulation of bone mass, bone loss, and osteoclast activity by cannabinoid receptors. Nat. Med., 22�May�2005 [e-pub ahead of print]. doi:10.1038/nm1255
||See Pryce et al. (2003).
||Studies of CB1 knockout mice have shown that CB1 is involved in the motivational properties of opiates and in the development of physical dependence on these drugs. In addition, CB1 knockouts were found to eat less than wild-type littermates after temporary food restriction, a behavior linked to the leptin-responsive neural circuitry. These mice also show strongly impaired extinction of aversive memories in auditory fear-conditioning tests.
Silencing of CB1 in mice (through genetic or pharmacological means) has also been shown to cause the retention of a large number of embryos in the oviduct, leading to pregnancy failure.
||SAGE KE News Focus:
"The Skeleton Goes to Pot"
Mouse Genome Informatics:
Online Mendelian Inheritance in Man:
Cannabinoid Receptor 1
regulation of bone mass
regulation of bone loss
June 15, 2005
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- G. Pryce, Z. Ahmed, D. J. Hankey, S. J. Jackson, J. L. Croxford, J. M. Pocock, C. Ledent, A. Petzold, A. J. Thompson, G. Giovannoni et al., Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126, 2191-2202 (2003).[Abstract/Free Full Text]
- H. Wang, Y. Guo, D. Wang, P. Kingsley, L. Marnett, S. Das, R. DuBois, S. Dey, Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nat. Med. 10, 1074-1080 (2004).[CrossRef][Medline]
CB1 Knockout Mice. Sci. Aging Knowl. Environ. 2005
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