CD36 Transgenic and Knockout Mice Models

Recent development of well-defined genetic models of CD36 deficiency and tissue-specific overexpression has added greatly to our understanding of the physiological role of CD36 as a mediator of FA uptake. Previous studies could not yield definitive data as a result of the complexity of the animal models used, which possessed polygenic aberrations. For example, in the SHR NIH CD36 deficiency was linked to insulin resistance while in the obese Zucker rat, upregulation of CD36 in adipocytes was...

Info

Suppression of HNF-4a-responsive genes Fig. 12.6 Suppression of HNF-4a responsive genes by carboxylic effectors of PPARa and HNF-4a. Suppression of HNF-4a-responsive genes may be mediated directly or indirectly by suppression of HNF-4a transcriptional activity or by displacement of HNF-4a from its cognate enhancer by activated PPARa RXR under conditions where PPARa RXR is tran-scriptionally non-productive, respectively. The PPARa-dependent indirect pathway requires the free acid form (RCOOH) of...

Sulfonylurea Receptor ABCC8SUR

Sulfonylurea Insulin Secretion

Familial persistent hyperinsulinemic hypoglycemia of infancy PHHI is characterized by unregulated insulin secretion from pancreatic beta cells. The defect has been localized to chromosome 11p15.1-p14, a chromosomal region containing the ABCC8 SUR1 gene and the KCNJ11 Kir6.2 gene 187 . Subsequently, causal mutations in the ABCC8 gene have been described in PHHI families 188 Tab. 3.2 however, no defects in the KCNJ11 gene have found so far. As described earlier in this chapter see Section 3.3.3 ,...

CD36 Gene Structure and Regulation

The CD36 gene consists of 15 exons encompassing more than 32 kilobases on the q11.2 band of human chromosome 7 33 . Both the N- and C-terminal transmembrane and cytoplasmic domains are encoded by single exons exon III and part of exon XIV , while the extracellular domain is divided among 11 exons IV-XIV . Recently, several mRNA transcripts arising from alternative splicing of coding exons in peripheral blood monocytes have been reported 34 . The protein products of these alternate forms have...

Retinal Degeneration and ABCA4 ABCR

Rod Photoreceptors

In addition to ABCA1, the ABCA4 ABCR gene located on chromosome 1p21 Tabs 3.1 and 3.2 is another example how several mutations in one ABC transporter gene can cause pleiotropic effects. Thus, many different clinical phenotypes, associated with various forms of eye degeneration, and the age of onset as well as disease severity are associated with distinct mutations in ABCA4 9 . As summarized in Tab. 3.2, ABCA4 has been found to be a causal gene for a series of retinal diseases. As an effort of...

References

Lublin, J. Biol. Chem. 1996, 271, 22315-22320. 2 M.A. Connelly, M. de la Llera-Moya, P. Monzo, P.G. Yancey, D. Drazul, G. Stoudt, N. Fournier, S.M. Klein, G. H. Rothblat, D. L. Williams, Biochemistry 2001, 40, 5249-5259. 3 A. Jochen, J. Hays, J. Lipid Res. 1993, 34, 1783-1792. 4 B. Podolsak, Thromb. Haemost. 1977, 37, 396-406. 5 D.E. Greenwalt, N.N. Tandon, G.A. Ja-mieson, Thromb. Haemost. 1991, 65, 1153. 6 A.S. Asch, I. Liu, F.M. Briccetti, J. W. Barnwell, F....

ABCA1 in Macrophage Lipid Transport

Lipid Transport

Several factors control the expression and activity of ABCA1. Induced cholesterol influx into macrophage cells has been shown to be a potent inducer of ABCA1 expression 40 . Since the cloning of the complete human and mouse ABCA1 genes, a number of transcriptional control elements acting via alternative promoters have been characterized 197-199 Fig. 3.6 . The ABCA1 upstream region contains a macrophage-specific promoter preceding exon 1. This sequence binds the repressors ZNF202 and USF1 2, as...

Cystic Fibrosis ABCC7CFTR

Nherf Dimer

Cystic fibrosis, caused by mutations in ABCC7 CFTR Tab. 3.2 is one of the most frequent inherited diseases in Caucasian populations with a prevalence of 1 900 to 1 2500, whereas African and Asian individuals are affected to a much lesser extent. Interestingly, a three base pair deletion AF508 accounts for 70-80 of the mutated alleles in northern European populations. The total number now comprises more than 1000 CFTR mutations The spectrum of the disease severity is dependent on the residual...

ABC Transporters involved in Hepatobiliary Transport

Monovalent Bile Salts Ntcp

The formation of bile is an elementary physiological function of the liver, which involves numerous transport proteins located in the basolateral sinusoidal and apical canalicular membranes of hepatocytes Fig. 3.9 . Bile, which is composed of bile salts, phospholipids, cholesterol, bilirubin and many other small molecules, is necessary for the micellar absorption of lipids from the intestine as well as for the excretion of endogenous and xenobiotic compounds 228 . The first step in...