Knockout mice described

An other notable example is the work described by Flerzyk et al. [31] where the effects of a Primatized antihuman CD4 monoclonal antibody on experimental metastases with B16 melanoma cells was studied, and an increase in the number of lung colonies was found. Enabling this work, a murine CD4 knockout mouse reconstituted with human CD4 had been described in the literature and was available for license by the sponsor [32], Moreover, in these mice, murine CD4 was faithfully replaced on T cells by human CD4, and the human protein mediated its physiologic function as an accessory binding protein in cellular and humoral immunity. 

Many examples of inhibitory presynaptic neuropeptide Y receptors have been found in tissues from experimental animals and humans (Table 3), based on experiments with each of the four techniques described in the Introduction (overflow experiments, electrophysiological techniques, pithed animals, electrically induced twitches in isolated tissues). For the identification of the receptors, the three peptides and modified (e.g., truncated) congeners (Figure 4) were the only tools for many years. More recently, selective antagonists (e.g., in the study by Schwertfeger et al. [2004] on the human heart) and knockout mice (e.g., in the study by Smith-White et al. [2002] on the mouse heart) have been used. According to most studies, only Y2 receptors serve as presynaptic neuropeptide Y receptors. 

The widespread presence of nicotinic receptors in the central nervous system coupled with the relative rarity of a classical synaptic role means that it is still difficult to describe a clear physiological role for these receptors. This is particularly true for receptors in presynaptic locations, for which the level and temporal pattern of exposure to the neurotransmitter are unknown. Approaches that are casting light on this problem include mouse knockout models and transmitter depletion by blockers of vesicular transport processes such as vesamicol the combination of these techniques has recently shown that normal evoked dopamine release in striatal slices is strongly dependent on endogenous cholinergic mechanisms that involve the activation of j32-containing nicotinic receptors (240). 

Male mice (age 14-16 wk and weight 20-30 g) are kept under 12-h hght/dark cycle with free access to water and food. A slow-releasing morphine peUet (25 mg) or placebo pellet (25 mg) (NIDA, Rockville, MD) was implanted subcutaneously in each mouse under isofluorene anesthesia. Mice with morphine pellets developed withdrawal syndrome after 4 d. On d 5, mice were sacrificed by cervical dislocation. Mu knockout mice and wild-type littermates in the experiments were described previously. The mouse brain was dissected rapidly and frozen immediately in liquid nitrogen. 

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