Mikael Bjursell
Publications 36
#1Alba Carreras (Sahlgrenska University Hospital)H-Index: 4
#2Luna Simona PaneH-Index: 2
Last.Marcello MarescaH-Index: 6
view all 20 authors...
Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target diseas...
1 CitationsSource
#1Stephen Lee (UCLA: University of California, Los Angeles)H-Index: 27
#2Christina Priest (UCLA: University of California, Los Angeles)H-Index: 1
Last.Cynthia Hong (UCLA: University of California, Los Angeles)H-Index: 31
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Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of diet-induced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specif...
#1Daniel Lindén (AstraZeneca)H-Index: 19
#2Andrea Ahnmark (AstraZeneca)H-Index: 8
Last.Stefano Romeo (Magna Græcia University)H-Index: 41
view all 24 authors...
Abstract Objective Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic liver disease. The progression of NAFLD, including nonalcoholic steatohepatitis (NASH), has a strong genetic component, and the most robust contributor is the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding the 148M protein sequence variant. We hypothesized that suppressing the expression of the PNPLA3 148M mutant protein would exert a beneficial effect on the ent...
9 CitationsSource
#1Alice E. Pollard (Imperial College London)H-Index: 1
#2Luís Martins (Imperial College London)H-Index: 1
Last.David Carling (Imperial College London)H-Index: 80
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Obesity results from a chronic imbalance between energy intake and energy output but remains difficult to prevent or treat in humans. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an important regulator of energy homeostasis1–3 and is a molecular target of drugs used for the treatment of metabolic diseases, including obesity4,5. Here we show that mice expressing a gain-of-function AMPK mutant6 display a change in morphology of subcutaneous white adipocytes that is reminiscent ...
1 CitationsSource
#1Pinar Akcakaya (AstraZeneca)H-Index: 3
#2Maggie L. Bobbin (Harvard University)H-Index: 4
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 22 authors...
CRISPR–Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1–6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe ‘verification of in vivo off-targets’ (VIVO), a highly sensitive strategy that can robustly identi...
48 CitationsSource
#1Christian JungH-Index: 45
#2Bernhard Wernly (University of Salzburg)H-Index: 7
Last.Qing-Dong Wang (AstraZeneca)H-Index: 24
view all 17 authors...
Abstract Background Oxytocin (Oxt) and its receptor (Oxtr) gene system has been implicated in cardiomyogenesis and cardioprotection; however, effects of chronic activation of Oxtr are not known. We generated and investigated transgenic (TG) mice that overexpress Oxtr specifically in the heart. Methods and Results Cardiac-specific overexpression of Oxtr was obtained by having the α-major histocompatibility complex promoter drive the mouse Oxtr gene (α-Mhc-Oxtr). Left ventricular (LV) function and...
1 CitationsSource
#1Pinar Akcakaya (AstraZeneca)H-Index: 3
#2Maggie L. Bobbin (Harvard University)H-Index: 1
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 22 authors...
CRISPR-Cas genome-editing nucleases hold substantial promise for human therapeutics but identifying unwanted off-target mutations remains an important requirement for clinical translation. For ex vivo therapeutic applications, previously published cell-based genome-wide methods provide potentially useful strategies to identify and quantify these off-target mutation sites. However, a well-validated method that can reliably identify off-targets in vivo has not been described to date, leaving the q...
4 CitationsSource
#1Mikael Bjursell (AstraZeneca)H-Index: 20
#2Michelle J. Porritt (AstraZeneca)H-Index: 4
Last.John Wiseman (AstraZeneca)H-Index: 4
view all 14 authors...
Abstract α1-antitrypsin (AAT) is a circulating serine protease inhibitor secreted from the liver and important in preventing proteolytic neutrophil elastase associated tissue damage, primarily in lungs. In humans, AAT is encoded by the SERPINA1 (hSERPINA1) gene in which a point mutation (commonly referred to as PiZ) causes aggregation of the miss-folded protein in hepatocytes resulting in subsequent liver damage. In an attempt to rescue the pathologic liver phenotype of a mouse model of human AA...
11 CitationsSource
#1Mikael BjursellH-Index: 20
#2Erik RybergH-Index: 9
Last.Stephan HjorthH-Index: 40
view all 6 authors...
10 CitationsSource
#1Maria Liljevald (AstraZeneca)H-Index: 3
#2Maria Rehnberg (AstraZeneca)H-Index: 2
Last.Johan Jirholt (AstraZeneca)H-Index: 11
view all 16 authors...
Abstract RORγ is a nuclear hormone receptor which controls polarization of naive CD4 + T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORγ has therapeutic potential for autoimmune diseases; however, this mechanism may potentially carry target-related safety risks, as mice deficient in Rorc, the gene encoding RORγ, develop T-cell lymphoma with 50% frequency. Due to the requirement of RORγ during development, the Rorc knockout (KO) animals lack secondary lymphoid organs and...
22 CitationsSource