Gene knockout mice

Ohtsu, H. Watanabe, T. (2003). New functions of histamine found in histidine decarboxylase gene knockout mice. Biochem. Biophys. Res. Commun. 305, 443-7. 

Eguchi, N., et at (2002). Sleep in transgenic and gene-knockout mice for... 

Transport by ASBT is electrogenic with a 2 1 ratio of Na rbile acids and membrane potential may regulate transport function. ASBT is essential for the enterohepatic circulation as shown by ASBT gene knockout mice that developed bile-acid malabsorption with no enterohepatic circulation. This is summarised in Figure 2.4. 

Mezey E, Reisine TD, Skirboll L, Beinfeld M, Kiss JZ (1985) Cholecystokinin in the medial parvocellular subdivision of the paraventricular nucleus coexistence with corticotropinreleasing hormone. Ann NY Acad Sci 448 152-156 Miller CC, Holmes PV, Edwards GL (2002) Area postrema lesions elevate NPY levels and decrease anxiety-related behavior in rats. Physiol Behav 77 135-140 Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takiguchi S, Takata Y, Kawanami T, Funakoshi A (2002) Anxiety-related behaviors in cholecystokinin-A, B, and AB receptor gene knockout mice in the plus-maze. Neurosci Lett 335 115-118... 

Miyasaka K, Kobayashi S, Ohta M, Kanai S, Yoshida Y, Nagata A, Matsui T, Noda T, Takuguchi S, Takata Y, Kawanami T, Funakoshi A (2002) Anxiety-related behaviors in cholecystokinin-A,B, and AB receptor gene knockout mice in the plus-maze. Neurosci Lett 335 115-118... 

Xi L, Das A, Zhao ZQ, Merino VF, Bader M, Kukreja RC (2008) Loss of myocardial ischemic postconditioning in adenosine A( and bradykinin B2 receptors gene knockout mice. Circulation 118(14 Suppl) S32-S37... 

The search for intestinal cholesterol transporters extended for many years, beginning with a debate about whether or not it was even a protein-facilitated process (4, 5). The pancreatic enzyme carboxyl ester lipase (CEL, also called cholesterol esterase) was believed to be important to this process (6,7) and several companies devoted considerable resources to the development and testing of compounds to inhibit CEL, with mixed results (8-10). These efforts were abandoned in the mid-1990s, however, after studies with gene-knockout mice demonstrated that the enzyme was important only for absorption of cholesteryl ester (11, 12), which is a minor component of dietary cholesterol and is present at very low levels in bile. Interestingly, CEL is also found in liver where it has been shown to affect HDL metabolism (13). Thus, it may ultimately play an important role in cholesterol metabolism and may yet prove to be a useful drug target for CVD treatment (Camarota and Howies, unpublished). 

Intestinal acyl-CoA cholesterol acyltransferase (ACAT-2, also present in liver), which esterifies free cholesterol with palmitic or oleic acid, is another enzyme that was identified early on as a potential target to inhibit cholesterol absorption because most cholesterol in chylomicrons is esterified before being secreted by enterocytes (6, 14). As for CEL, various inhibitors of this enzyme were also developed and tested with mixed results (10, 15-17). However, the importance of ACAT-2 was later confirmed by studies of gene-knockout mice, which exhibit markedly reduced cholesterol absorption and atherosclerosis when fed Western diet (18). Nonetheless, progress in developing effective ACAT inhibitors has been slow, in part because of concerns about the potential for deleterious systemic effects resulting from inhibition of the more widely expressed ACAT-1 (19). Despite these... 

Studies with gene-knockout mice (30) as well as chemical inhibitors (31) have shown that decreasing activity of... 

At present, we can induce CML in mice with high efficiency, shown by 100% induction of CML in mice (14). The same CML disease could be induced in most of the inbred mouse strain including C57BL/6, BALB/c, and viable gene knockout mice strains (15). Because all recipients develop CML with a short latency (about 3 weeks), this provides an excellent model for evaluating therapeutic agents for CML treatment (15). As CML is derived from the hematopoietic stem cells which harbor BCR-ABL oncogene, CML leukemia stem cells can also be studied in this model (15). In conclusion, this retroviral model system pro-... 

ROLES OF THE HISTAMINERGIC NEUROTRANSMISSION ON METHAMPHETAMINE-INDUCED LOCOMOTOR SENSITIZATION AND REWARD A STUDY OF RECEPTORS GENE KNOCKOUT MICE... 

A. Changes of Locomotor Activity in Histamine Receptor Gene Knockout Mice by METH Administration... 

B. METH-Induced CPP in Single Histamine Receptors Genes Knockout Mice... 

Fig. 1. Effect of repeated administration of METH or saline on the locomotor activity in WT and histamine receptors genes double (HI and H3) and triple (HI, H2, H3) knockout mice. The locomotor activity of mice was measured for 3 h after administration of METH (1 mg/kg, closed circle) or saline (open circle) in the WT (A), H1/H3 (B), H1/H2/H3 (C) receptor gene knockout mice. Mice were injected seven times once in every 3 days with saline or METH (1 mg/kg, i.p.). After drug-free intervals of 7 days, saline or METH were rechallenged. Each value represents the mean S.E.M. of six mice.

Fig. 2. The increased locomotor activity by repeated treatment with METH when compared to saline in each histamine receptor genotypes. The ratios were calculated from the total locomotor activity countin Fig. 1. The WT (closed column), H1/H3 (diagonal line of column), H1/H2/H3 (open column) receptor gene knockout mice.

Fig. 3. Comparison of METH-induced CPP in single histamine receptor gene knockout mice. Mice were injected 1 mg/kg of METH or saline every other day, and confined for 30 min to a compartment designed to condition the place preference. The CPP score were calculated using the staying time of mouse in each compartment for 15 min before and after the conditioning. Each value represents the mean S.E.M. of 6-18 mice. Statistical analysis was performed by means of one-way ANOVA followed by Tukey s test ( p < 0.05, p < 0.01).

Iwabuchi, K., Kubota, Y., Ito, C., Watanabe, T., Watanabe, T., and Yanai, K. (2004). Methamphetamine and brain histamine A study using histamine-related gene knockout mice. Ann. N. T. Acad. Sci. 1025, 129-134. 

Gonzalez, F. J. NCI, NIH Transgenic mice, gene knockout mice, and cytochrome P-450 function Division of Cancer Etiology... 

Yanai K, Mobarakeh Jl, Kuramasu A, Sakurada S (2003) Roles of histamine receptors in pain perception a study using receptors gene knockout mice. Nippon Yakurigaku Zasshi 122 ... 

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