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Genetics

  • 271 Articles
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Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice
Paul A. Crossey, … , Claire C. Pillai, John P. Miell
Paul A. Crossey, … , Claire C. Pillai, John P. Miell
Published August 1, 2002
Citation Information: J Clin Invest. 2002;110(3):411-418. https://doi.org/10.1172/JCI10077.
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Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice

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Abstract

Research Article

Authors

Paul A. Crossey, Claire C. Pillai, John P. Miell

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The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis
Manabu Shirai, … , Keiko Yamauchi-Takihara, Yoshihiro Takihara
Manabu Shirai, … , Keiko Yamauchi-Takihara, Yoshihiro Takihara
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):177-184. https://doi.org/10.1172/JCI14839.
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The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis

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Abstract

Research Article

Authors

Manabu Shirai, Tomoaki Osugi, Hideyuki Koga, Yoshikazu Kaji, Eiki Takimoto, Issei Komuro, Junichi Hara, Takeshi Miwa, Keiko Yamauchi-Takihara, Yoshihiro Takihara

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Signaling through estrogen receptors modulates telomerase activity in human prostate cancer
Simona Nanni, … , Alfredo Pontecorvi, Antonella Farsetti
Simona Nanni, … , Alfredo Pontecorvi, Antonella Farsetti
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):219-227. https://doi.org/10.1172/JCI15552.
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Signaling through estrogen receptors modulates telomerase activity in human prostate cancer

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Abstract

Research Article

Authors

Simona Nanni, Michela Narducci, Linda Della Pietra, Fabiola Moretti, Annalisa Grasselli, Piero De Carli, Ada Sacchi, Alfredo Pontecorvi, Antonella Farsetti

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Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome
Duarte C. Barral, … , Kalwant S. Authi, Miguel C. Seabra
Duarte C. Barral, … , Kalwant S. Authi, Miguel C. Seabra
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):247-257. https://doi.org/10.1172/JCI15058.
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Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome

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Abstract

Research Article

Authors

Duarte C. Barral, José S. Ramalho, Ross Anders, Alistair N. Hume, Holly J. Knapton, Tanya Tolmachova, Lucy M. Collinson, David Goulding, Kalwant S. Authi, Miguel C. Seabra

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Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride
Charles R. Roe, … , France David, Henri Brunengraber
Charles R. Roe, … , France David, Henri Brunengraber
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):259-269. https://doi.org/10.1172/JCI15311.
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Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride

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Abstract

Research Article

Authors

Charles R. Roe, Lawrence Sweetman, Diane S. Roe, France David, Henri Brunengraber

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The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy
Junichi Sadoshima, … , Dorothy E. Vatner, Stephen F. Vatner
Junichi Sadoshima, … , Dorothy E. Vatner, Stephen F. Vatner
Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):271-279. https://doi.org/10.1172/JCI14938.
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The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy

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Abstract

Research Article

Authors

Junichi Sadoshima, Olivier Montagne, Qian Wang, Guiping Yang, Jill Warden, Jing Liu, Gen Takagi, Vijaya Karoor, Chull Hong, Gary L. Johnson, Dorothy E. Vatner, Stephen F. Vatner

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Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype
Clive R. Pullinger, … , Mary J. Malloy, John P. Kane
Clive R. Pullinger, … , Mary J. Malloy, John P. Kane
Published July 1, 2002
Citation Information: J Clin Invest. 2002;110(1):109-117. https://doi.org/10.1172/JCI15387.
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Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype

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Abstract

Research Article

Authors

Clive R. Pullinger, Celeste Eng, Gerald Salen, Sarah Shefer, Ashok K. Batta, Sandra K. Erickson, Andrea Verhagen, Christopher R. Rivera, Sean J. Mulvihill, Mary J. Malloy, John P. Kane

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Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells
Amit Choudhury, … , David L. Marks, Richard E. Pagano
Amit Choudhury, … , David L. Marks, Richard E. Pagano
Published June 15, 2002
Citation Information: J Clin Invest. 2002;109(12):1541-1550. https://doi.org/10.1172/JCI15420.
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Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells

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Abstract

We recently showed that human skin fibroblasts internalize fluorescent analogues of the glycosphingolipids lactosylceramide and globoside almost exclusively by a clathrin-independent mechanism involving caveolae. In contrast, a sphingomyelin analogue is internalized approximately equally via clathrin-dependent and caveolar routes. Here, we further characterized the caveolar pathway for glycosphingolipids, showing that Golgi targeting of sphingolipids internalized via caveolae required microtubules and phosphoinositol 3-kinases and was inhibited in cells expressing dominant-negative Rab7 and Rab9 constructs. In addition, overexpression of wild-type Rab7 or Rab9 (but not Rab11) in Niemann-Pick type C (NP-C) lipid storage disease fibroblasts resulted in correction of lipid trafficking defects, including restoration of Golgi targeting of fluorescent lactosylceramide and endogenous GM1 ganglioside, and a dramatic reduction in intracellular cholesterol stores. Our results demonstrate a role for Rab7 and Rab9 in the Golgi targeting of glycosphingolipids and suggest a new therapeutic approach for restoring normal lipid trafficking in NP-C cells.

Authors

Amit Choudhury, Michel Dominguez, Vishwajeet Puri, Deepak K. Sharma, Keishi Narita, Christine L. Wheatley, David L. Marks, Richard E. Pagano

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Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent
Manuel Yepes, … , Thomas H. Bugge, Daniel A. Lawrence
Manuel Yepes, … , Thomas H. Bugge, Daniel A. Lawrence
Published June 15, 2002
Citation Information: J Clin Invest. 2002;109(12):1571-1578. https://doi.org/10.1172/JCI14308.
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Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent

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Abstract

Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase expressed in the CNS during events that require neuronal plasticity. In this study we demonstrate that endogenous tPA mediates the progression of kainic acid–induced (KA-induced) seizures by promoting the synchronization of neuronal activity required for seizure spreading, and that, unlike KA-induced cell death, this activity is plasminogen-independent. Specifically, seizure induction by KA injection into the amygdala induces tPA activity and cell death in both hippocampi, and unilateral treatment of rats with neuroserpin, a natural inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi. Inhibition of tPA within the hippocampus by neuroserpin treatment does not prevent seizure onset but instead markedly delays the progression of seizure activity in both rats and wild-type mice. In tPA-deficient mice, seizure progression is significantly delayed, and neuroserpin treatment does not further delay seizure spreading. In contrast, plasminogen-deficient mice show a pattern of seizure spreading and a response to neuroserpin that is similar to that of wild-type animals. These findings indicate that tPA acts on a substrate other than plasminogen and that the effects of neuroserpin on seizure progression and neuronal cell survival are mediated through the inhibition of tPA.

Authors

Manuel Yepes, Maria Sandkvist, Timothy A. Coleman, Elizabeth Moore, Jiang-Young Wu, David Mitola, Thomas H. Bugge, Daniel A. Lawrence

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Biotin dependency due to a defect in biotin transport
Rebecca Mardach, … , Stephen Cederbaum, Donald M. Mock
Rebecca Mardach, … , Stephen Cederbaum, Donald M. Mock
Published June 15, 2002
Citation Information: J Clin Invest. 2002;109(12):1617-1623. https://doi.org/10.1172/JCI13138.
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Biotin dependency due to a defect in biotin transport

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Abstract

We describe a 3-year-old boy with biotin dependency not caused by biotinidase, holocarboxylase synthetase, or nutritional biotin deficiency. We sought to define the mechanism of his biotin dependency. The child became acutely encephalopathic at age 18 months. Urinary organic acids indicated deficiency of several biotin-dependent carboxylases. Symptoms improved rapidly following biotin supplementation. Serum biotinidase activity and Biotinidase gene sequence were normal. Activities of biotin-dependent carboxylases in PBMCs and cultured skin fibroblasts were normal, excluding biotin holocarboxylase synthetase deficiency. Despite extracellular biotin sufficiency, biotin withdrawal caused recurrent abnormal organic aciduria, indicating intracellular biotin deficiency. Biotin uptake rates into fresh PBMCs from the child and into his PBMCs transformed with Epstein Barr virus were about 10% of normal fresh and transformed control cells, respectively. For fresh and transformed PBMCs from his parents, biotin uptake rates were consistent with heterozygosity for an autosomal recessive genetic defect. Increased biotin breakdown was ruled out, as were artifacts of biotin supplementation and generalized defects in membrane permeability for biotin. These results provide evidence for a novel genetic defect in biotin transport. This child is the first known with this defect, which should now be included in the identified causes of biotin dependency.

Authors

Rebecca Mardach, Janos Zempleni, Barry Wolf, Martin J. Cannon, Michael L. Jennings, Sally Cress, Jane Boylan, Susan Roth, Stephen Cederbaum, Donald M. Mock

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A hop, exon skip, and a jump for muscular dystrophy
Quan Gao and colleagues developed an exon skipping strategy that generates a truncated, functional γ-sarcoglycan protein and improves defects in muscular dystrophy models…
Published October 12, 2015
Scientific Show StopperGenetics

A curve in the spine
Shunmoogum Patten and colleagues identify variants of POC5 that are associated with idiopathic scoliosis…
Published February 2, 2015
Scientific Show StopperGenetics
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