Genomic Structure and Organization of the HumanrBATGene (SLC3A1)

Purroy, Jesús; Bisceglia, Luigi; Calonge, Marı́a Julia; Zelante, Leopoldo; Testar, Xavier; Zorzano, António; Estivill, Xavier; Palacı́n, Manuel; Nunes, Virginia; Gasparini, Paolo

doi:10.1006/geno.1996.0552

Cited by 21 publications

(10 citation statements)

References 5 publications

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“…This normal dog was homozygous for the 7-5 allele of the hexanucleotide repeat area while its affected littermate was homozygous for the 8-5 allele. As expected based on the human SLC3A1 gene structure (Endsley et al 1997;Pras et al 1996;Purroy et al 1996), the canine SLC3A1 gene is divided into ten exons, with the coding region interrupted by introns at places analogous to those in the human gene. The sequences of the exons of the normal Newfoundland dog were identical to the entire open reading frame of the normal cloned cDNA sequence, with the exception of the lengths of the hexanucleotide repeats in exon 1 (6-6 as opposed to 7-5).…”

Section: Isolation and Characterization Of The Canine Slc3a1 Genementioning

confidence: 97%

Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

et al. 2000

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Cystinuria is an inherited renal and intestinal disease characterized by defective amino acid reabsorption and cystine urolithiasis. Different forms of the disease, designated type I and non-type I in cystinuric humans, can be distinguished clinically and biochemically, and have been associated with mutations in the SLC3A1 (rBAT) and SLC7A9 genes, respectively. Type I cystinuria is the most common form and is inherited as an autosomal recessive trait in humans. Cystinuria has been recognized in more than 60 breeds of dogs and a severe form, resembling type I cystinuria, has been characterized in the Newfoundland breed. Here we report the cloning and sequencing of the canine SLC3A1 cDNA and gene, and the identification of a nonsense mutation in exon 2 of the gene in cystinuric Newfoundland dogs. A mutation-specific test was developed for the diagnosis and control of cystinuria in Newfoundland dogs. In cystinuric dogs of six other breeds, either heterozygosity at the SLC3A1 locus or lack of mutations in the coding region of the SLC3A1 gene were observed, indicating that cystinuria is genetically heterogeneous in dogs, as it is in humans. The canine homologue of human type I cystinuria provides the opportunity to use a large animal model to investigate molecular approaches for the treatment of cystinuria and other renal tubular diseases.

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Section: Isolation and Characterization Of The Canine Slc3a1 Genementioning

confidence: 97%

Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

et al. 2000

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“…The SLC3A1 gene spans ~46 kb and includes 10 coding exons [22,23]. The longest transcript (ENST00000260649) is 2989 bp long, the resulting protein rBAT (ENSP00000260649) consists of 685 amino acids.…”

Section: The Slc3a1 and Slc7a9 Genes And The Amino Acid Transporter Smentioning

confidence: 99%

Cystinuria: an inborn cause of urolithiasis

Eggermann

Venghaus

Zerres

2012

Orphanet Journal of Rare Diseases

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Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy subunit rBAT of a renal b0,+ transporter while SLC7A9 (chromosome 19q12) encodes its interacting light subunit b0,+AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.

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“…These characteristics identified the expressed transport activity as amino acid transport system y + L and are consistent with other evidence suggesting that 4F2hc might have a role in the basal membrane transport of cationic amino acids in intestine, kidney and placenta. Mutations in the human BAT gene cause the genetic disease cystinuria [18][19][20][21][22][23][24][25]. By analogy, 4F2hc is a plausible candidate for a second human amino acid transport disorder, lysinuric protein intolerance [68].…”

Section: Discussionmentioning

confidence: 99%

“…intestinal\renal brush border membrane transport of cationic amino acids and cystine [18][19][20]. Mis-sense mutations of human BAT have been demonstrated in cystinuria chromosomes [21][22][23][24][25], and expression of the most common mutation found in cystinuria patients [Met-467 changed to threonine (Met467Thr)] decreases transport activity in Xenopus oocytes by 90 % [21].…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional expression of a cDNA from rat jejunal epithelium encoding a protein (4F2hc) with system y+L amino acid transport activity

Yao

Muzyka

Elliott

et al. 1998

Biochemical Journal

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Two different protein families, designated CAT (cationic amino acid transporter) and BAT (broad-specificity amino acid transporter) mediate the plasma membrane transport of cationic amino acids in animal cells. CAT transporters have 12-14 transmembrane domains and are selective for cationic amino acids. BAT proteins, in contrast, have one to four transmembrane domains and induce the transport of both cationic and zwitterionic amino acids when expressed in Xenopus oocytes. Mutations in the human BAT gene cause type I cystinuria, a disease affecting the ability of intestinal and renal brush border membranes to transport cationic amino acids and cystine. We have used functional expression cloning in oocytes to isolate a BAT-related cDNA from rat jejunal epithelium. The cDNA encodes the rat 4F2 heavy chain (4F2hc) cell-surface antigen, a 527-residue (60 kDa) protein that is 26% identical in amino acid sequence with rat renal BAT (also known as NBAT/D2). Expression of rat jejunal 4F2hc in oocytes induced the lysine-inhibitable Na+-dependent influx of leucine and the leucine-inhibitable Na+-independent influx of lysine. Lysine efflux was stimulated by extracellular (Na+ plus leucine). These characteristics identify the expressed amino acid transport activity as system y+L, a transporter that has been implicated in basal membrane transport of cationic amino acids in intestine, kidney and placenta.

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Genomic Structure and Organization of the HumanrBATGene (SLC3A1)

Cited by 21 publications

References 5 publications

Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs

Cystinuria: an inborn cause of urolithiasis

Cloning and functional expression of a cDNA from rat jejunal epithelium encoding a protein (4F2hc) with system y+L amino acid transport activity

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