Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persi...

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Autores principales:	Yuan Yan Sin, Laurel L Ballantyne, Kamalika Mukherjee, Tim St Amand, Lianna Kyriakopoulou, Andreas Schulze, Colin D Funk
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ea10de58c854949becce57c4833c47d
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spelling	oai:doaj.org-article:9ea10de58c854949becce57c4833c47d2021-11-18T08:48:25ZInducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.1932-620310.1371/journal.pone.0080001https://doaj.org/article/9ea10de58c854949becce57c4833c47d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24224027/?tool=EBIhttps://doaj.org/toc/1932-6203Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2) mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.Yuan Yan SinLaurel L BallantyneKamalika MukherjeeTim St AmandLianna KyriakopoulouAndreas SchulzeColin D FunkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80001 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuan Yan Sin Laurel L Ballantyne Kamalika Mukherjee Tim St Amand Lianna Kyriakopoulou Andreas Schulze Colin D Funk Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
description	Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1), which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2) mice. The resulting mice (Arg-Cre) die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.
format	article
author	Yuan Yan Sin Laurel L Ballantyne Kamalika Mukherjee Tim St Amand Lianna Kyriakopoulou Andreas Schulze Colin D Funk
author_facet	Yuan Yan Sin Laurel L Ballantyne Kamalika Mukherjee Tim St Amand Lianna Kyriakopoulou Andreas Schulze Colin D Funk
author_sort	Yuan Yan Sin
title	Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
title_short	Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
title_full	Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
title_fullStr	Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
title_full_unstemmed	Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
title_sort	inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9ea10de58c854949becce57c4833c47d
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Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

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