[ Back to EurekAlert! ] Public release date: 17-Jan-2008
[ | E-mail Share Share ]

Contact: Karen Honey
Journal of Clinical Investigation

JCI table of contents: Jan. 17, 2008

EDITOR'S PICK: Engineered mice provide insight into Alzheimer disease

One factor that determines how at risk an individual is of developing late-onset Alzheimer disease (AD) is the version of the APOE gene that they carry — those carrying the gene that enables them to make the apoE4 form of the apoE protein are at increased risk and those carrying the gene that enables them to make the apoE2 form are at decreased risk. It has been hypothesized that increasing the amount of lipid (fat) associated with apoE by overexpressing the protein ABCA1 might decrease amyloid deposition in the brain, the hallmark of AD. Evidence to support this hypothesis has now been generated in mice by David Holtzman and colleagues at Washington University School of Medicine, St Louis.

In this study, mice that provide a model of AD (PDAPP mice) were engineered to overexpress the protein ABCA1 in the brain. These mice had characteristics almost identical to PDAPP mice lacking apoE — they had decreased amyloid deposition in the brain compared with normal PDAPP mice. As the PDAPP mice overexpressing ABCA1 in the brain were shown to have increased amounts of lipid associated with apoE, the authors concluded the hypothesis that an ABCA1-mediated increase in the amount of lipid associated with apoE would decrease amyloid deposition in the brain was correct. Furthermore, they suggested that approaches to increase the function of ABCA1 in the brain might be of benefit to individuals with, or at risk of developing, AD.

TITLE: Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease

AUTHOR CONTACT: David M. Holtzman
Washington University School of Medicine, St Louis, Missouri, USA.
Phone: (314) 362-9872; Fax: (314) 362-1771; E-mail: holtzman@neuro.wustl.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33622

EDITOR'S PICK: Scratching an itch: neutralizing IL-22 prevents psoriasis in mice

Psoriasis, which is a chronic disease characterized by the development of red, scaly, raised skin lesions, affects approximately 2% of the population of countries of the Western world. A new study by Lynette Fouser and colleagues at Wyeth Research, Cambridge, Massachusetts, has provided evidence that the soluble molecule IL-22 is central to the development of disease in a mouse model of psoriasis. Antibodies that neutralized IL-22 were found to prevent the development of psoriasis-like disease, reducing thickening of the skin, inflammatory infiltrates, and expression of Th17 cytokines. Conversely administration of IL-22 into the skin of normal mice induced the expression of genes associated with the development of psoriasis-like skin lesions. These data led the authors to suggest that antagonizing IL-22 might provide a new approach to treating individuals with psoriasis.

TITLE: IL-22 is required for Th17 cell–mediated pathology in a mouse model of psoriasis-like skin inflammation

AUTHOR CONTACT: Lynette A. Fouser
Wyeth Research, Cambridge, Massachusetts, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33263

METABOLIC DISEASE: Seeing is believing: visualizing inflammation in fat tissue

Individuals who are obese are at increased risk of developing a combination of medical disorders associated with type 2 diabetes and heart disease known as the metabolic syndrome. Recent studies have suggested that adipose (fat) tissue obesity induces an inflammatory state that is crucial to the development of the metabolic syndrome.

In a new study, Satoshi Nishimura, Ichiro Manabe, and colleagues at the University of Tokyo, Japan have developed a technique based on confocal laser microscopy to visualize cellular interactions within mouse adipose tissue in vivo with high spatiotemporal resolution. Changes indicative of inflammation were observed in the adipose tissue of both mice that were obese through genetic mutations and mice that were obese as a result of being fed a high-fat diet. In addition, endothelial cells of the adipose tissue could be seen interacting with inflammatory cells known as macrophages, indicating a central role for interplay between these two cell types in the activation of inflammation within the adipose tissue. The authors therefore concluded that adipose tissue obesity is an inflammatory disease and suggested that this technique might allow the efficacy of potential therapeutics for the treatment of individuals with diseases stemming from adipose tissue obesity to be evaluated in vivo in mice.

TITLE: In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue

AUTHOR CONTACT: Satoshi Nishimura
University of Tokyo, Tokyo, Japan.
Phone: 81-3-3815-5411; Fax: 81-3-3814-0021; E-mail: snishi-tky@umin.ac.jp.

Ichiro Manabe
University of Tokyo, Tokyo, Japan.
Phone: 81-3-3815-5411; Fax: 81-3-3814-0021; E-mail: manabe-tky@umin.ac.jp.

View the PDF of this article at: https://www.the-jci.org/article.php?id=33328

NEPHROLOGY: Factor I complements the kidney

Membranoproliferative glomerulonephritis type II (MPGN2) is an inflammatory kidney disease. It is characterized by the presence of the protein complement C3 along glomerular basement membranes (GBMs), which are part of the basic filtration structures of the kidney. Although two proteins (factor H and factor I) regulate one pathway by which C3 can be activated, only deficiency in factor H is associated with MPGN2. A possible explanation for this discordance has now been provided by Matthew Pickering and colleagues at Imperial College, United Kingdom, who showed in mice that the generation of activated C3 fragments in the circulation by factor I was crucial for the development of MPGN2 associated with factor H deficiency.

In the study, mice lacking either factor I or both factor H and factor I were found not to develop MPGN2-like disease. However, when mice lacking both factor H and factor I were administered factor I, C3 fragments were detected in the plasma and C3 was deposited on the GBM. Further analysis using transplantation studies revealed that the C3 deposited on the GBM was derived from the plasma, and led the authors to suggest that either preventing the generation of C3 fragments in the circulation or sequestering them might abrogate C3 deposition on the GBM.

TITLE: Factor I is required for the development of membranoproliferative glomerulonephritis in factor H–deficient mice

AUTHOR CONTACT: Matthew C. Pickering
Imperial College, Hammersmith Campus, London, United Kingdom.
Phone: 44-208-383-2398; Fax: 44-208-743-3109; E-mail: matthew.pickering@imperial.ac.uk.

View the PDF of this article at: https://www.the-jci.org/article.php?id=32525


[ Back to EurekAlert! ] [ | E-mail Share Share ]


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.