In human alpha 1-antitrypsin deficiency, homozygous carriers of the Z (E324K) mutation in the gene SERPINA1 have insufficient circulating alpha 1-antitrypsin and are predisposed to emphysema. Misfolding and accumulation of the mutant protein in hepatocytes also causes endoplasmic reticulum stress and underpins long-term liver damage. Here, we describe transgenic zebrafish (Danio rerio) expressing the wildtype or the Z mutant form of human alpha 1-antitrypsin in hepatocytes. As observed in afflicted humans, and in rodent models, about 80% less alpha 1-antitrypsin is evident in the circulation of zebrafish expressing the Z mutant. Although these zebrafish also show signs of liver stress, they do not accumulate alpha 1-antitrypsin in hepatocytes. This new zebrafish model will provide useful insights into understanding and treatment of alpha 1-antitrypsin deficiency.
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Borel, Florie
Sun, Huaming
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Sun, Huaming
Zieger, Marina
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Zieger, Marina
Cox, Andrew
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Cox, Andrew
Cardozo, Brynn
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Cardozo, Brynn
Li, Weiying
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Li, Weiying
Oliveira, Gabriella
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Oliveira, Gabriella
Davis, Airiel
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Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Davis, Airiel
Gruntman, Alisha
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Gruntman, Alisha
Flotte, Terence R.
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Flotte, Terence R.
Brodsky, Michael H.
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Univ Massachusetts, Dept Mol Cell & Canc Biol, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Brodsky, Michael H.
Hoffman, Andrew M.
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Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Hoffman, Andrew M.
Elmallah, Mai K.
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Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Elmallah, Mai K.
Mueller, Christian
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机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Borel, Florie
Sun, Huaming
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机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Sun, Huaming
Zieger, Marina
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机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Zieger, Marina
Cox, Andrew
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机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Cox, Andrew
Cardozo, Brynn
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机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Cardozo, Brynn
Li, Weiying
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h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Li, Weiying
Oliveira, Gabriella
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h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Oliveira, Gabriella
Davis, Airiel
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Davis, Airiel
Gruntman, Alisha
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Gruntman, Alisha
Flotte, Terence R.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Flotte, Terence R.
Brodsky, Michael H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Dept Mol Cell & Canc Biol, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Brodsky, Michael H.
Hoffman, Andrew M.
论文数: 0引用数: 0
h-index: 0
机构:
Tufts Univ, Cummings Sch Vet Med, Grafton, MA 01536 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Hoffman, Andrew M.
Elmallah, Mai K.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Elmallah, Mai K.
Mueller, Christian
论文数: 0引用数: 0
h-index: 0
机构:
Univ Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA
Univ Massachusetts, Dept Pediat, Med Sch, Worcester, MA 01605 USAUniv Massachusetts, Horae Gene Therapy Ctr, Med Sch, Worcester, MA 01605 USA