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Title: Inducible Slc7a7 Knockout Mouse Model Recapitulates Lysinuric Protein Intolerance Disease
Author: Bodoy i Salvans, Susanna
Sotillo, Fernando
Espino-Guarch, Meritxell
Sperandeo, Maria Pia
Ormazabal Herrero, Aida
Zorzano Olarte, Antonio
Sebastio, Gianfranco
Artuch Iriberri, Rafael
Palacín Prieto, Manuel
Keywords: Malalties rares
Rare diseases
Issue Date: 24-Oct-2019
Publisher: MDPI
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: International Journal of Molecular Sciences, 2019, vol. 20, num. 21, p. 1-15
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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