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Li Q , Jiang Q , LaRusso J , Klement JF , Sartorelli AC , Belinsky MG , Kruh GD , Uitto J
Targeted ablation of Abcc1 or Abcc3 in Abcc6(-/-) mice does not modify the ectopic mineralization process
Experimental Dermatology. 2007 Oct;16(10) :853-859
PMID: ISI:000249276000009   
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Abstract
Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues, with considerable intra- and interfamiliar phenotypic variability. PXE is caused by mutations in the ABCC6 gene, which encodes a transporter protein, MRP6, and targeted ablation of Abcc6 in mice recapitulates the manifestations of PXE. In this study, we examined the hypothesis that the expression of other members of the Abcc family may be altered in Abcc6 null mice, possibly explaining the phenotypic variability because of the functional overlap of these transporters. Analysis of the transcript levels of Abcc1-10 and 12 in the liver of Abcc6 (-/-) mice by quantitative RT-PCR indicated that the levels of other C family mRNAs were not significantly different from wild-type mice. Next, we developed Abcc6/1(-/-) and Abcc6/3(-/-) double null mice and examined them for tissue mineralization. Histopathologic examination, coupled with computerized morphometric analysis, and chemical assay of calcium x phosphate product in the muzzle skin of Abcc1(-/-) and Abcc3(-/-) mice did not reveal evidence of mineralization. Abcc6/1(-/-) and Abcc6/3(-/-) double knock-out mice exhibited connective tissue mineralization similar to that in Abcc6 (-/-) mice. These results emphasize the importance of the Abcc6 gene in the ectopic mineralization process and further suggest that other members of the Abcc family, particularly Abcc1 and Abcc3, do not modulate the effects of Abcc6 in this mouse model.
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ISI Document Delivery No.: 207UG Times Cited: 0 Cited Reference Count: 45 Cited References: AHERRAHROU Z, 2007, PHYSIOL GENOMICS, V28, P203 BELINSKY MG, 1999, BRIT J CANCER, V80, P1342 BELINSKY MG, 2002, CANCER RES, V62, P6172 BELINSKY MG, 2005, MOL PHARMACOL, V68, P160 BERGEN AAB, 2000, NAT GENET, V25, P228 CHU XY, 2006, J PHARMACOL EXP THER, V317, P579 CHUTKOW WA, 2001, P NATL ACAD SCI USA, V98, P11760 DEELEY RG, 2006, PHYSIOL REV, V86, P849 ELMAADAWY S, 2003, CONNECT TISSUE RE S1, V44, P272 GORGELS TGMF, 2005, HUM MOL GENET, V14, P1763 GRUBB BR, 1999, PHYSIOL REV, V79, P193 HENDIG D, 2006, CLIN CHEM, V52, P227 HIROHASHI T, 1998, MOL PHARMACOL, V53, P1068 HOSOKAWA S, 1992, LAB ANIM SCI, V42, P27 ILIAS A, 2002, J BIOL CHEM, V277, P16860 IVANDIC BT, 1996, P NATL ACAD SCI USA, V93, P5483 IVANDIC BT, 2001, PHYSIOL GENOMICS, V6, P137 JAHNENDECHENT W, 1997, J BIOL CHEM, V272, P31496 JANSEN PLM, 1985, HEPATOLOGY, V5, P573 JIANG QJ, 2007, J INVEST DERMATOL, V127, P1392 JOHNSON BM, 2006, DRUG METAB DISPOS, V34, P556 KARTENBECK J, 1996, HEPATOLOGY, V23, P1061 KLEMENT JF, 2005, MOL CELL BIOL, V25, P8299 KONIG J, 1999, HEPATOLOGY, V29, P1156 KOOL M, 1999, CANCER RES, V59, P175 KORFF S, 2006, PHYSIOL GENOMICS, V25, P387 KRUH GD, 2007, CANCER METAST REV, V26, P5 LESAUX O, 2000, NAT GENET, V25, P223 LORICO A, 1997, CANCER RES, V57, P5238 LUO GB, 1997, NATURE, V386, P78 MIKSCH S, 2005, HUM MUTAT, V26, P235 NELDNER KH, 1988, CLIN DERMATOL, V6, P1 PAULUSMA CC, 1997, HEPATOLOGY, V25, P1539 RENIE WA, 1984, AM J MED GENET, V19, P235 RINGPFEIL F, 2000, P NATL ACAD SCI USA, V97, P6001 RINGPFEIL F, 2001, EXP DERMATOL, V10, P221 RINGPFEIL F, 2006, J INVEST DERMATOL, V126, P782 SCHEFFER GL, 2002, LAB INVEST, V82, P515 SEGHERS V, 2000, J BIOL CHEM, V275, P9270 SHIOTA C, 2002, J BIOL CHEM, V277, P37176 STRUK B, 2000, J MOL MED-JMM, V78, P282 UITTO J, 2005, TRENDS MOL MED, V11, P341 WADA M, 1998, HUM MOL GENET, V7, P203 WANG W, 2005, MOL CELL BIOL, V25, P312 WIJNHOLDS J, 1997, NAT MED, V3, P1275