Sci. Aging Knowl. Environ., 15 June 2005
Vol. 2005, Issue 24, p. tg4
[DOI: 10.1126/sageke.2005.24.tg4]

GENETICALLY ALTERED MICE

CB1 Knockout Mice

http://sageke.sciencemag.org/cgi/content/full/2005/24/tg4


Mouse CB1 knockout
Genetic background See Pryce et al. (2003).
Gene changed 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.
Phenotype 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.
Primary reference 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
Additional references See below.
Source See Pryce et al. (2003).
Other comments 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.
Other links SAGE KE News Focus:
"The Skeleton Goes to Pot"
Mouse Genome Informatics:
Cnr1
Online Mendelian Inheritance in Man:
Cannabinoid Receptor 1
Keywords cannabinoid receptor
regulation of bone mass
regulation of bone loss
osteoclast activity
Prepared by Michael Russell


June 15, 2005
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Citation: CB1 Knockout Mice. Sci. Aging Knowl. Environ. 2005 (24), tg4 (2005).








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