Richard D Palmiter

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The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these(More)
The murine ZnT3 gene was cloned by virtue of its homology to the ZnT2 gene, which encodes a membrane protein that facilitates sequestration of zinc in endosomal vesicles. ZnT-3 protein is predicted to have six transmembrane domains and shares 52% amino acid identity with ZnT-2, with the homology extending throughout the two sequences. Human ZnT-3 cDNAs were(More)
The mammalian protein ZnT3 resides on synaptic vesicle membranes of zinc-containing neurons, suggesting its possible role in vesicular zinc transport. We show here that histochemically reactive zinc, corresponding to the zinc found within synaptic vesicles, was undetectable in the brains of mice with targeted disruption of the ZnT3 gene. Total zinc levels(More)
Leptin is the primary signal through which the hypothalamus senses nutritional state and modulates food intake and energy balance. Leptin reduces food intake by upregulating anorexigenic (appetite-reducing) neuropeptides, such as alpha-melanocyte-stimulating hormone, and downregulating orexigenic (appetite-stimulating) factors, primarily neuropeptide Y.(More)
Hypothalamic neurons that express neuropeptide Y (NPY) and agouti-related protein (AgRP) are thought to be critical regulators of feeding behavior and body weight. To determine whether NPY/AgRP neurons are essential in mice, we targeted the human diphtheria toxin receptor to the Agrp locus, which allows temporally controlled ablation of NPY/AgRP neurons to(More)
Microinjection of foreign DNA into fertilized mammalian eggs is a convenient means of introducing genes into the germ line. Some of the more important parameters that influence successful integration of foreign DNA into mouse chromosomes are described. The effects of DNA concentration, size, and form (supercoiled vs. linear with a variety of different ends)(More)
Catecholamines such as noradrenaline and adrenaline have been implicated in numerous physiological processes but, although catecholamine synthesis begins at mid-gestation, previous studies have provided little evidence for any role in early development. Furthermore, there are several case reports of humans with noradrenaline deficiency. To investigate this,(More)
Dopamine neurons in the ventral tegmental area (VTA) play an important role in the motivational systems underlying drug addiction, and recent work has suggested that they also release the excitatory neurotransmitter glutamate. To assess a physiological role for glutamate corelease, we disrupted the expression of vesicular glutamate transporter 2 selectively(More)
The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann-Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of(More)
Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH function in noradrenergic cells. These DA-deficient (DA-/-) mice were born at expected frequency but became hypoactive and stopped feeding a few weeks after birth. Midbrain dopaminergic neurons,(More)