Gene Targeting

Publication Title: 
Free Radical Biology & Medicine

Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.

Elia, A. J.
Parkes, T. L.
Kirby, K.
St George-Hyslop, P.
Boulianne, G. L.
Phillips, J. P.
Hilliker, A. J.
Publication Title: 
Archives of Pharmacal Research

Caloric restriction prolongs the lifespan of many species. Therefore, investigators have researched the usefulness of caloric restriction for healthy lifespan extension. Sirt1, an NAD(+)-dependent deacetylase, was identified as a molecule necessary for caloric restriction-related anti-aging strategies. Sirt1 functions as an intracellular energy sensor to detect the concentration of NAD(+), and controls in vivo metabolic changes under caloric restriction and starvation through its deacetylase activity to many targets including histones, nuclear transcriptional factors, and enzymes.

Kume, Shinji
Kitada, Munehiro
Kanasaki, Keizo
Maegawa, Hiroshi
Koya, Daisuke
Publication Title: 
Biological Psychiatry

The mammalian brain poses a formidable challenge to the study and treatment of neuropsychiatric diseases, owing to the complex interaction of genetic, epigenetic, and circuit-level mechanisms underlying pathogenesis. Technologies that facilitate functional dissection of distinct brain circuits are necessary for systematic identification of disease origin and therapy.

Mei, Yuan
Zhang, Feng
Publication Title: 
Molecular Neurobiology

Epigenetic and regulatory elements provide an additional layer of complexity to the heterogeneity of anxiety disorders. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that have recently drawn interest as epigenetic modulators of gene expression in psychiatric disorders. miRNAs elicit their effects by binding to target messenger RNAs (mRNAs) and hindering translation or accelerating degradation. Considering their role in neuronal differentiation and synaptic plasticity, miRNAs have opened up new investigative avenues in the aetiology and treatment of anxiety disorders.

Malan-M¸ller, Stefanie
Hemmings, SÓan Megan Joanna
Seedat, Soraya
Publication Title: 
The Journal of Biological Chemistry

Loss of ABCA1 activity in Tangier disease (TD) is associated with abnormal apoB lipoprotein (Lp) metabolism in addition to the complete absence of high density lipoprotein (HDL). We used hepatocyte-specific ABCA1 knock-out (HSKO) mice to test the hypothesis that hepatic ABCA1 plays dual roles in regulating Lp metabolism and nascent HDL formation. HSKO mice recapitulated the TD lipid phenotype with postprandial hypertriglyceridemia, markedly decreased LDL, and near absence of HDL.

Chung, Soonkyu
Timmins, Jenelle M.
Duong, Myngan
Degirolamo, Chiara
Rong, Shunxing
Sawyer, Janet K.
Singaraja, Roshni R.
Hayden, Michael R.
Maeda, Nobuyo
Rudel, Lawrence L.
Shelness, Gregory S.
Parks, John S.
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