Effects of genetic backgrounds on hyperbilirubinemia in radixin-deficient mice due to different expression levels of Mrp3.
ERM (ezrin/radixin/moesin) proteins are organizers of apical actin cortical layer in general. We previously reported that the knockout of radixin resulted in Rdx(-/-) mice with displacement/loss of the canalicular transporter Mrp2, giving rise to Dubin-Johnson syndrome-like conjugated hyperbilirubinemia in the mixed genetic background (C57BL/6-129/Sv) (Kikuchi, et al. (2002) Nature Genetics 31, 320-325). However, when these mice were kept under mixed genetic background for years (late mixed backgrounds; LMB), the conjugated hyperbilirubinemia gradually became inconspicuous, while evidence of liver injury increased. We examined the effect of genetic background by backcrossing LMB Rdx(-/-) mice to C57BL/6 and 129/Sv wild type mice with the result that the Rdx(-/-) congenic mice regained hyperbilirubinemia with reduced hepatocellular damage. As revealed by immunofluorescence and western blots, the localization/expression of apical transporters, Mrp2, CD26, P-gps, and Bsep were not influenced by backcrossing, though those of a basolateral transporter, Mrp3, were strikingly increased by backcrossing.
Fukumoto
Kanehisa
K
Department of Cell Biology, Kyoto University Faculty of Medicine, Yoshida-Konoe, Kyoto 606-8501, Japan.
Kikuchi
Shojiro
S
Itoh
Norio
N
Tamura
Atsushi
A
Hata
Masaki
M
Yamagishi
Hisakazu
H
Tsukita
Shoichiro
S
Tsukita
Sachiko
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000378:metabolism; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001648:Bile Canaliculi / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D003598:Cytoskeletal Proteins; D018819:Dipeptidyl Peptidase 4; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C490549:Abcb11 protein, mouse; C071776:radixin; C114462:multidrug resistance-associated protein 3