Mouse mutants

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

In cerebellar Purkinje cells, a TTX-sensitive inward current is elicited, when the membrane was partially repolarized after strong depolarization. This resurgent current contributes to high-frequency repetitive firing of Purkinje neurons. The resurgent current results from open channel block by the cytoplasmic tail of the (34 subunit. The med Nav 1.6 mutant mice show defective synaptic transmission in the neuromuscular junction and degeneration of cerebellar Purkinje cells. 

Thiele TE, Miura Gl, Marsh DJ, et al Neurobiological responses to ethanol in mutant mice lacking neuropeptide Y or the Y5 receptor. Pharmacol Biochem Behav 67 683-691, 2000... 

The in vivo relevance and biological importance of in vitro observations about mast cell function, as well as the contributions of mast cells towards the expression of particular biological responses (such as various models of anaphylaxis) in vivo, can be assessed using c-kit mutant mice (e.g., WBB6Fi-FCit or mice) that virtually lack mast cell populations. Mice with mutations of c-kit [6,11] or mutations that affect KIT expression [12-14] have other abnormalities of phenotype besides a mast cell deficiency. However, the mast cell deficiency of these mice can be selectively repaired by the adoptive transfer of genetically compatible, in vitro-derived... 

Kitamura Y, Go S, Hatanaka K Decrease of mast cells in W/W" mice and their increase by bone marrow transplantation. Blood 1978 52 447-452. Grimbaldeston MA, Chen CC. Piliponsky AM, Tsai M. Tam SY, Galh SJ Mast cell-deficient W-sash c-kit mutant mice as a model for investigating... 

The proposal that NO or its reactant products mediate toxicity in the brain remains controversial in part because of the use of non-selective agents such as those listed above that block NO formation in neuronal, glial, and vascular compartments. Nevertheless, a major area of research has been into the potential role of NO in neuronal excitotoxicity. Functional deficits following cerebral ischaemia are consistently reduced by blockers of NOS and in mutant mice deficient in NOS activity, infarct volumes were significantly smaller one to three days after cerebral artery occlusion, and the neurological deficits were less than those in normal mice. Changes in blood flow or vascular anatomy did not account for these differences. By contrast, infarct size in the mutant became larger... 

Fletcher, CF, Lutz, CM, O Sullivan, TN, Shaughnessy Jr, JD, Hawkes, R, Frankel, WN, Copeland, NG and Jenkins, NA (1996) Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87 607-617. 

Nocka, K., Majumder, S., Chabot, B., Ray, P., Cervone, M., Bernstein, A., and Besmer, P. (1989). Expression of the c-kit gene products in known cellular targets of W mutant mice-evidence for an impaired c-kit kinase in mutant mice. Genes Dev. 3 816-826. 

Tajima, Y Onoue, H Kitamura, Y., and Nishimune, Y. (1991). Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in Sid mutant mice. Development 113 1031-1035. 

Pan, Y., Kislinger, T., Gramolini, A.O., Zvaritch, E., Kranias, E.G., MacLennan, D.H., Emih, A. (2004). Identification of biochemical adaptations in hyper- or hypocontractile hearts from phospholamban mutant mice by expression proteomics. Proc. Natl. Acad. Sci. USA 101, 2241-2246. 

Hamase, K., Inoue, T., Morikawa, A., Konno, R., Zaitsu, K. (2001). Determination of free d-proline and D-leucine in the brains of mutant mice lacking D-amino acid oxidase activity. Anal. Biochem. 298, 253-258. 

Studies in knockout mice indicate that the p2 nAChRs are necessary for nicotine self-administration, DA-dependent locomotor activation, and nicotine-associated enhancement of NAc DA release.40-51 53 Combined with studies showing that antagonism of the high-affinity nAChRs block self-administration,44-54 it would appear that p2 nAChRs are particularly critical for nicotine reinforcement. Unlike wild-type mice that self-administer both cocaine and nicotine, p2 nAChR-null mutant mice learn to self-administer cocaine normally, but stop bar pressing as though receiving saline when cocaine is switched to nicotine.40 Self-administration of VTA nicotine and associated DA release is rescued, however, in p2 nAChR knockout mice with lentiviral-mediated expression of P2 subunit DNA in the VTA.55 Whereas several configurations of the p2 nAChRs exist at the... 

Epping-Jordan, M.P., Picciotto, M.R., Changeux, J.P., Pich, E.M. Assessment of nicotinic acetylcholine receptor subunit contributions to nicotine self-administration in mutant mice. Psychopharmacology (Berlin). 147 25, 1999. 

Chiamulera, C., Epping-Jordan, M.R, Zocchi, A. et al. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat. Neurosci. 4 873, 2001. 

Hiroi, N., Brown, J.R., Haile, C.N. et al. FosB mutant mice loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine s psychomotor and rewarding effects. Proc. Natl. Acad. Sci. U.S.A. 94 10397, 1997. 

Mizoguchi, A., Mizoguchi, E., Chiba, C., Spiekermann, G.M., Tonegawa, S., Nagler-Anderson, C. and Bhan, A.K. (1996) Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease. Journal of Experimental Medicine 183, 847-856. 

Minowa T et al. Proteomic analysis of the small intestine and colon epithelia of adenomatous polyposis coli gene-mutant mice by two-dimensional gel electrophoresis. Electrophoresis 2000 21 1782—1786. 

Deltour L, Foglio MH, Deuster G. Metabolic deficiencies in alcohol dehydrogenase Adhl, Adh3, and Adh4 null mutant mice Overlapping roles of Adhl and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. J Biol Chem 1999 274 16796-16801. 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

Xu, M., Moratalla, R., Gold, L. H. etal. Dopamine D1 receptor mutant mice are deficient in striatal expression of dyn-orphin and in dopamine-mediated behavioral responses. Cell 79 729-742,1994. 

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