Wangjing Ke

The University of Arizona, Tucson, Arizona, United States

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Publications (3)8.25 Total impact

  • Ivan Borbon · Erin Campbell · Wangjing Ke · Robert P Erickson ·
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    ABSTRACT: We have previously shown that decreased dosage of Niemann-Pick C1 (Npc1) protein, caused by heterozygosity at the null mutation, Npc1 (nih), locus, causes altered lipid metabolism in mice. When studied on the "lean" BALB/cJ genetic background, the decreased protein was associated with no weight changes in either males or females when on a regular diet but increased weights and adiposity when on a high fat diet Jelinek et al. (Obesity 18: 1457-1459, 2010, Gene 491:128-134, 2012). When the heterozygotes were studied on a mixed C57BL/6J, BALB/cJ background, increased weight and adiposity were also found on a regular diet (sexes pooled Jelinek et al. [Hum Molec Genet 20:312-321, 2011]). We find somewhat different results when the hypomorphic Npc1 mutation, Npc1 (nmf164), is studied on a pure C57BL/6J, "metabolic syndrome" genetic background with male, but not female, heterozygotes having lower weights on the regular diet. The result does not seem to be due to the difference in the two mutations as heterozygous Npc1 (nmf164) mice on the BALB/cJ background acted like the null mutant heterozygotes. Studies of glucose tolerance, liver enzymes, liver triglycerides and fat deposition, and adipose tissue caveolin 1 levels did not disclose reasons for these differing results.
    Journal of applied genetics 05/2012; 53(3):323-30. DOI:10.1007/s13353-012-0099-8 · 1.48 Impact Factor
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    ABSTRACT: Niemann-Pick C1 (NPC) disease, also known as "juvenile Alzheimer's disease", is a disease in which alterations in intracellular cholesterol trafficking occur. The contribution of various CNS cell types to the neurodegeneration has been of much interest. We have previously shown that expression of the normal gene only in fibrillary astrocytes could extend survival of Npc1-/- mice over 3-fold (Zhang et al., 2008 [13]). We have now studied expression only in neurons or in both neurons and fibrillary astrocytes. Neuron-only expression resulted in survivals of over a year (>5-fold) but motor symptoms started at about 6 months. As reflected in weight gain, this especially affected females who weighed less than wild-type starting at about 10 weeks while male differences in weight are delayed. Expression in both cell types led to a nearly normal phenotype with motor symptoms developing at about ten months and increased survival times. Purkinje cell loss was slowed, but severe, in both NSE- and NSE-GFAP-Npc1, transgenic Npc1-/- mice. MRI studies showed that myelination of the long tracts was significantly improved in NSE-Npc1 transgenics, perhaps less than in GFAP-Npc1 transgenics, and not differently than in the double transgenics. Memory was improved in both single and double transgenics. Somatic disease had not been ameliorated and lungs were massively infiltrated with foamy macrophages at 10 months. Our results suggest that neuron-only expression does not completely prevent neurodegeneration and that the addition of astrocyte expression decreases the rate/degree of decline.
    Journal of Alzheimer's disease: JAD 04/2012; 30(4):875-87. DOI:10.3233/JAD-2012-120199 · 4.15 Impact Factor
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    ABSTRACT: Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight was markedly increased; using the flexiVent small animal ventilator (SCIREQ, Inc.), we find inspiratory capacity, elastance and hysterisivity to be increased while resistance was not changed. Cholesterol measurements show a doubling of lung cholesterol levels. Collagen is also increased. Treatment of Npc1(-/-) mice with hydroxypropyl-β-cyclodextrin (HPBCD), despite efficacious effects in brain and liver, results in little difference from age-matched controls (using a CNS-expressed transgene to extend the life expectancy of the Npc1(-/-) mice) for these variables.
    Molecular Genetics and Metabolism 03/2011; 103(2):142-7. DOI:10.1016/j.ymgme.2011.03.001 · 2.63 Impact Factor