53 research outputs found
Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease
Lysinuric protein intolerance (LPI) is a rare autosomal disease caused by defective cationic amino acid (CAA) transport due to mutations in SLC7A7, which encodes for the y+LAT1 transporter. LPI patients suffer from a wide variety of symptoms, which range from failure to thrive, hyperammonemia, and nephropathy to pulmonar alveolar proteinosis (PAP), a potentially life-threatening complication. Hyperammonemia is currently prevented by citrulline supplementation. However, the full impact of this treatment is not completely understood. In contrast, there is no defined therapy for the multiple reported complications of LPI, including PAP, for which bronchoalveolar lavages do not prevent progression of the disease. The lack of a viable LPI model prompted us to generate a tamoxifen-inducible Slc7a7 knockout mouse (Slc7a7-/-). The Slc7a7-/- model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of CAA, hypoargininemia and hyperammonemia. Interestingly, the Slc7a7-/- mice also develops PAP and neurological impairment. We observed that citrulline treatment improves the metabolic derangement and survival. On the basis of our findings, the Slc7a7-/- model emerges as a promising tool to further study the complexity of LPI, including its immune-like complications, and to design evidence-based therapies to halt its progression
Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene.
A 68 bp insertion found in a homocystinuric patient is a common variant and is skipped by alternative splicing of the cystathionine b-synthase mRNA
Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects.
Cationic amino acid transport through system y+L in erythrocytes of patients with lysinuric protein intolerance.
Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance
SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance
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