title: Cystine transport activity of heterozygous rBAT mutants expressed in Xenopus oocytes.
abstract: The rBAT gene encodes a transport protein for cystine and dibasic amino acids. It is a candidate gene for type I cystinuria, a genetic disorder inherited as an autosomal-recessive trait. Recently, several mutations in rBAT from Japanese patients with cystinuria have been reported from our laboratory. Some of these patients were heterozygous, which appears to be inconsistent with the previous concept that mutations in rBAT are recessive. To investigate the function of heterozygous mutants, we introduced these mutations into rBAT gene and analyzed the transport activity of cystine associated with the mutants in Xenopus oocytes. Co-injection of the mutant T1037C (L346P) and the polymorphism G1854A (M6181) into Xenopus oocytes produced a transport activity of 67.9% of the wild type. Oocytes co-injected with T2017C (C673R) and wild type had a transport activity of 70.3% of the wild type. These findings indicate that the heterozygous mutants show decreased transport activity compared to wild-type rBAT. Further, some mutants in rBAT may show decreased cystine transport activity even in heterozygous condition, which may contribute to stone-forming cystinuria.
authors.affiliation: Department of Urology, Chiba University School of Medicine, Japan. VYS00450@nifty.ne.jp
authors.forename: Masanari
authors.initials: M
authors.lastname: Ishihara
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Akakura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Egoshi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mikami
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
authors.forename: Haruo
authors.initials: H
authors.lastname: Ito
mesh_terms: D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003553:Cystine / Q000378:metabolism*; D003555:Cystinuria / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D018075:RNA, Complementary; D014545:Urinary Calculi / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D018075:RNA, Complementary; C499489:SLC7A9 protein, human; D003553:Cystine