Null mutants

For some of the GLUT isotypes, the phenotype of null mutants is known. Haploinsufficiency of the GLUT1 in... 

Manstein, D.J., Titus, M.A., DeLozanne, A., and Spudich, J.A. (1989). Gene replacement in Dic-tyostelium Generation of myosin null mutants. EMBO J. 8, 923-932. 

Wessels. D., Soil, D.R.. Knecht, D.. Loomis. W.F., De Lozanne. A., Spudich, J. (1989). Myosin IB null mutants of Dictyostelium exhibit abnormalities in motility. Cell Mot. Cytoskel. 20,301-315. 

Other homeobox gene targeting experiments have resulted in more dramatic developmental defects. Homozygous //ox-1.5 null mutants showed a number of alterations (Chisaka and Capecchi, 1991). The mice died at or shortly after birth, apparently from circulation and/or pulmonary problems. These animals showed hypertrophy of the atria and... 

Winston N J 1997 Stability of cyclin B protein during meiotic maturation and the first mitotic cell division in mouse oocytes. Biol Cell 89 211-219 Winston NJ, Maro B 1995 Calmodulin-dependent protein kinase II is activated transiently in ethanol-stimulated mouse oocytes. Dev Biol 170 350-352 Winston NJ, Bourgain-Guglielmetti F, Ciemerych MA et al 2000 Early development of mouse embryos null mutant for the cyclin A2 gene occurs in the absence of maternally derived cyclin A2 gene products. Dev Biol 223 139-153... 

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... 

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. 

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. 

Holmes, A., Hollon, T. R., Gleason, T. C. etal. Behavioral characterization of dopamine D5 receptor null mutant mice. Behav. Neurosci. 115 1129-1144,2001. 

The fact that null mutants in most CSN subunits lack the deneddylation activity in the presence of excess CSN5 supports the fact that CSN5 alone is inactive in deneddylation [61]. So far, the exact role of deneddylation is questionable (see below). 

Salminen O, Drapeau J, McIntosh JM, CoUins AC, Marks MJ, Grady SR (2007) Pharmacology of a-conotoxin Mil-sensitive subtypes of nicotinic acetylcholine receptors isolated by breeding of null mutant mice. Mol Pharmacol 71 1563-1571... 

Fig. 5 Dose-response curves for discriminative stimulus effects of nicotine in wild-type (filled circle) and knockout (open circle) mice trained with nicotine (0.8mg kg ), (a) shows results for 32 null mutant and control mice from Shoaib et al, (2002) whereas (b) shows corresponding results for a nuU mutants and their wild-type controls from Stolerman et al, 2004, Discriminative responding on the drug-appropriate lever is expressed as a percentage of the total numbers of responses on both levers. All data shown as means s,e,m, from 5-min extinction tests (n = 8-12). Figure 4a was published in Shoaib et al. (2002) The role of nicotinic receptor beta-2 subunits in nicotine discrimination and conditioned taste aversion. Copyright Elsevier Fig, 4b was published in Stolerman et al, (2004), The role of nicotinic receptor alpha subunits in nicotine discrimination. Copyright Elsevier...

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