TY  - JOUR
A1  - Beckmann, Nadine
A1  - Kadow, Stephanie
A1  - Schumacher, Fabian
A1  - Goethert, Joachim R.
A1  - Kesper, Stefanie
A1  - Draeger, Annette
A1  - Schulz-Schaeffer, Walter J.
A1  - Wang, Jiang
A1  - Becker, Jan U.
A1  - Kramer, Melanie
A1  - Kuehn, Claudine
A1  - Kleuser, Burkhard
A1  - Becker, Katrin Anne
A1  - Gulbins, Erich
A1  - Carpinteiro, Alexander
T1  - Pathological manifestations of Farber disease in a new mouse model
JF  - Biological chemistry
N2  - Farber disease (FD) is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of FD is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of FD and ceramide accumulation. Asah1(tmEx1) mice were generated by deletion of the acid ceramidase signal peptide sequence. The effects on lysosomal targeting and activity of the enzyme were assessed. Ceramide and sphingomyelin levels were quantified by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and disease manifestations in several organ systems were analyzed by histology and biochemistry. We show that deletion of the signal peptide sequence disrupts lysosomal targeting and enzyme activity, resulting in ceramide and sphingomyelin accumulation. The affected mice fail to thrive and die early. Histiocytic infiltrations were observed in many tissues, as well as lung inflammation, liver fibrosis, muscular disease manifestations and mild kidney injury. Our new mouse model mirrors human FD and thus offers further insights into the pathogenesis of this disease. In the future, it may also facilitate the development of urgently needed therapies.
KW  - acid ceramidase
KW  - ceramide
KW  - Farber disease
KW  - lysosomal storage disorders
Y1  - 2018
U6  - https://doi.org/10.1515/hsz-2018-0170
SN  - 1431-6730
SN  - 1437-4315
VL  - 399
IS  - 10
SP  - 1183
EP  - 1202
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Cheng, Shifeng
A1  - van den Bergh, Erik
A1  - Zeng, Peng
A1  - Zhong, Xiao
A1  - Xu, Jiajia
A1  - Liu, Xin
A1  - Hofberger, Johannes
A1  - de Bruijn, Suzanne
A1  - Bhide, Amey S.
A1  - Kuelahoglu, Canan
A1  - Bian, Chao
A1  - Chen, Jing
A1  - Fan, Guangyi
A1  - Kaufmann, Kerstin
A1  - Hall, Jocelyn C.
A1  - Becker, Annette
A1  - Bräutigam, Andrea
A1  - Weber, Andreas P. M.
A1  - Shi, Chengcheng
A1  - Zheng, Zhijun
A1  - Li, Wujiao
A1  - Lv, Mingju
A1  - Tao, Yimin
A1  - Wang, Junyi
A1  - Zou, Hongfeng
A1  - Quan, Zhiwu
A1  - Hibberd, Julian M.
A1  - Zhang, Gengyun
A1  - Zhu, Xin-Guang
A1  - Xu, Xun
A1  - Schranz, M. Eric
T1  - The Tarenaya hassleriana Genome Provides insight Into Reproductive Trait and Genome Evolution of Crucifers
JF  - The plant cell
N2  - The Brassicaceae, including Arabidopsis thaliana and Brassica crops, is unmatched among plants in its wealth of genomic and functional molecular data and has long served as a model for understanding gene, genome, and trait evolution. However, genome information from a phylogenetic outgroup that is essential for inferring directionality of evolutionary change has been lacking. We therefore sequenced the genome of the spider flower (Tarenaya hassleriana) from the Brassicaceae sister family, the Cleomaceae. By comparative analysis of the two lineages, we show that genome evolution following ancient polyploidy and gene duplication events affect reproductively important traits. We found an ancient genome triplication in Tarenaya (Th-alpha) that is independent of the Brassicaceae-specific duplication (At-alpha) and nested Brassica (Br-a) triplication. To showcase the potential of sister lineage genome analysis, we investigated the state of floral developmental genes and show Brassica retains twice as many floral MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR) genes as Tarenaya that likely contribute to morphological diversity in Brassica. We also performed synteny analysis of gene families that confer self-incompatibility in Brassicaceae and found that the critical SERINE RECEPTOR KINASE receptor gene is derived from a lineage-specific tandem duplication. The T. hassleriana genome will facilitate future research toward elucidating the evolutionary history of Brassicaceae genomes.
Y1  - 2013
U6  - https://doi.org/10.1105/tpc.113.113480
SN  - 1040-4651
VL  - 25
IS  - 8
SP  - 2813
EP  - 2830
PB  - American Society of Plant Physiologists
CY  - Rockville
ER  - 
TY  - JOUR
A1  - Henry, Brian D.
A1  - Neill, Daniel R.
A1  - Becker, Katrin Anne
A1  - Gore, Suzanna
A1  - Bricio-Moreno, Laura
A1  - Ziobro, Regan
A1  - Edwards, Michael J.
A1  - Muehlemann, Kathrin
A1  - Steinmann, Joerg
A1  - Kleuser, Burkhard
A1  - Japtok, Lukasz
A1  - Luginbuehl, Miriam
A1  - Wolfmeier, Heidi
A1  - Scherag, Andre
A1  - Gulbins, Erich
A1  - Kadioglu, Aras
A1  - Draeger, Annette
A1  - Babiychuk, Eduard B.
T1  - Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice
JF  - Nature biotechnology : the science and business of biotechnology
N2  - Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.
Y1  - 2015
U6  - https://doi.org/10.1038/nbt.3037
SN  - 1087-0156
SN  - 1546-1696
VL  - 33
IS  - 1
SP  - 81
EP  - U295
PB  - Nature Publ. Group
CY  - New York
ER  -