Null mutation

Mice homozygous for an ETA receptor gene disruption show craniofacial malformations, such as cleft palate, micrognathia, microtia and microglossia. ETA (—/—) mice die shortly after birth due to respiratory failure. Mice with an ET-l-null mutation show the same cranciofacial malformations and, in addition, cardiovascular disorders (e.g. septal defects, abnormal cardial outflow tract, aortic arch and subclavian arteries). 

Whiteaker, P., Marks, M.J., Grady, S.R. et al. Pharmacological and null mutation approaches reveal nicotinic receptor diversity. Eur. J. Pharmacol. 393 123, 2000. 

Acetylcholine receptor deficiency. The degree of disease severity may vary from mild to very severe. In general, patients harboring low-expressor or even homozygous null mutations in the AChR subunit may experience... 

Some of the molecules responsible for hair-cell transduction have been identified. A few key molecules, some already described, have been identified as part of the transduction complex (Fig. 51-6). Myosin molecules clearly play essential roles, and hair cells express a variety of myosin isoforms. Because it is located at the tips of the stereocilia, near the tip-link anchors, myosin-1 c is the best candidate for the adaptation motor. Selective inhibition of a sensitized myosin- lc mutant with an ADP analog proved that this myosin participates in adaptation [14], although contribution by other myosins has yet to be ruled out. For example, mice with near-null mutations in myosin-7a have defects in auditory transduction that are consistent with alterations in the adaptation machinery, suggesting a central role for this myosin too [15]. 

Kozel, P. J. et al. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. /. Biol. Chem. 273 18693-18696,1998. 

BURBULIS, I.E., IACOBUCCI, M., SHIRLEY, B.W., A null mutation in the first enzyme of flavonoid biosynthesis does not affect male fertility in Arabidopsis, Plant Cell, 1996, 8,1013-1025. 

Periasamy M, Reed TD, Liu LH et al 1999 Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J Biol Chem 274 2556—2562... 

Febbraio, A., Abumrad, N.A., Hajjar, D.P., Sharma, K., Cheng, W., Pearce, S.F., and SUverstein, R.L., 1999, A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism, 7. Biot. Chem. 274 19055-19062. 

Kedmi M, Orr-Urtreger A (2007) Differential brain transcriptome of beta4 nAChR subunit-deficient mice is it the effect of the null mutation or the background strain Physiol Genomics 28 213-222... 

D., Chambon, P., Crabtree, G., and Magnuson, T. (2000) A Brgl null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol. Cell 6, 1287-1295. 

Upregulation of CREB could play an important role in the actions of antidepressant treatment. To directly test this hypothesis, the influence of CREB expression in models of depression has been examined. For these studies, the expression of CREB or a dominant-negative mutant of CREB (mCREB) is increased by viral mediated gene transfer or by inducible transgenic expression. In addition, the influence of null mutation of one isoform, a-CREB, on behavior has been studied. Viral expression of wild-type CREB in the hippocampus, where antidepressant treatment increases CREB, results in an antidepressantlike effect in the forced swim (FST) and learned helplessness (LH) paradigms (Chen et al. 2001). The results demonstrate that increased expression of CREB is sufficient to produce an antidepressant effect and support the hypothesis that this transcription factor is an important target of antidepressant treatment. 

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