ABSTRACT
BRADFORD B.LOWELL, VEDRANA S.SUSULIC1, DANICA GRUJIC2 AND MORIKO ITO3 Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA 1 Present address: Wyeth-Ayerst Research, CN 8000, Princeton, NJ 08543, USA
3.1 Introduction
Given that ß3-adrenoreceptors (ß3AR) are abundantly expressed on white and brown adipocytes of rodents, and that ß3AR-selective agonists have potent effects on the function of white and brown adipocytes, it has been presumed that ß3AR play a critical role in mediating effects of the sympathetic nervous system on white and brown adipocytes. However, it has been difficult to test this hypothesis critically, given the general unavailability of ß3ARselective blockers. As a means of assessing the functional importance of ß3AR, our laboratory (Susulic et al., 1995) and another group (Revelli et al., 1997) have used gene targeting to create mice which lack ß3AR. Like any method, the gene knockout approach has advantages and disadvantages. Since gene knockout mice have a complete and selective absence of ß3AR, there are no concerns regarding the incompleteness or non-specificity of ‘blockade’. However, because ß3AR are absent from the first day of embryonic life, questions regarding long-term compensation for loss of ß3AR arise. Despite this and other potential limitations, the gene knockout approach is one of many important tools for assessing adrenoreceptor function in vivo. By generating gene knockout mice lacking a given receptor, it is possible to establish unequivocally the relationship between a cloned receptor and pharmacologically defined activities-an issue which is sometimes a source of controversy.
