A5027520924- CRISPR and Genetic Engineering
- Stress Responses and Cortisol
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Animal Genetics and Reproduction
- Adipose Tissue and Metabolism
- Developmental Biology and Gene Regulation
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- RNA Interference and Gene Delivery
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Neuroendocrine regulation and behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Hormonal Regulation and Hypertension
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
Helmholtz Zentrum München
2016-2025
Technical University of Munich
2016-2025
Munich Cluster for Systems Neurology
2016-2025
German Center for Neurodegenerative Diseases
2016-2025
Center for Environmental Health
2005-2024
Max Planck Institute of Psychiatry
2009-2023
Ludwig-Maximilians-Universität München
2014-2023
Institute of Groundwater Ecology
1997-2022
Institute of Bioinformatics and Systems Biology
1996-2022
Weihenstephan-Triesdorf University of Applied Sciences
2012-2021
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and publicly available genome-wide collection mouse knockouts would be significantly enabling for biomedical discovery. To date, published exist only about 10% genes. Furthermore, many these are limited utility because they have not been made or phenotyped standardized ways, freely to researchers. It is time harness new technologies efficiencies production mount high-throughput international effort...
Abstract Mutations in the cytosine‐5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities mice human. How post‐transcriptional methylation contributes to human disease is currently unknown. By comparing gene expression data with global methylomes patient fibroblasts NSun2‐deficient mice, we find that loss of increases angiogenin‐mediated endonucleolytic cleavage transfer RNAs ( tRNA ) leading an accumulation 5′ ‐derived small fragments. Accumulation fragments...
ABSTRACT During mouse development, the homeobox-containing gene En-1 is specifically expressed across mid-hindbrain junction, ventral ectoderm of limb buds, and in regions hindbrain, spinal cord, somites somite-derived tissues. To address function during embryogenesis, we have generated mice homozygous for a targeted deletion homeobox. mutant died shortly after birth exhibited multiple developmental defects. In brains newborn mutants, most colliculi cerebellum were missing third fourth...
Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, thus play a pivotal role in pathophysiology disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating the cellular defense against oxygen radicals. At present, relatively little is known about contribution of individual enzymes to redox metabolism different cell types. To begin address this question, we generated characterized mice...
The mouse inbred line C57BL/6J is widely used in genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using C57BL/6N strain to generate null alleles for all genes. Hence both strains now studies. Here we perform a comprehensive genomic phenotypic analysis of two identify differences that may influence their underlying mechanisms.We undertake sequence comparisons...
Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes recessive Parkinson disease (PD). Studies on loss function overexpression implicate PINK1 in apoptosis, abnormal morphology, impaired dopamine release motor deficits. However, fundamental mechanism underlying these various phenotypes remains to be clarified. Using fruit fly mouse models we show that deficiency or clinical mutations impact Complex I respiratory chain, resulting...
The related mouse Engrailed genes En-1 and En-2 are expressed from the one- approximately five-somite stages, respectively, in a similar presumptive mid-hindbrain domain. However, mutations produce different phenotypes. mutant mice die at birth with large deletion, whereas mutants viable, cerebellar defects. To determine whether these contrasting phenotypes reflect differences temporal expression or biochemical activity of En proteins, coding sequences were replaced by gene targeting. This...
Astrocytes are thought to play a variety of key roles in the adult brain, such as their participation synaptic transmission, wound healing upon brain injury, and neurogenesis. However, elucidate these functions vivo has been difficult because lack astrocyte-specific gene targeting. Here we show that inducible form Cre (CreERT2) expressed locus glutamate transporter (GLAST) allows precisely timed deletion astrocytes well radial glial cells at earlier developmental stages. Moreover, postnatal...
We describe a new mouse frameshift mutation (Pax2(1Neu)) with 1-bp insertion in the Pax2 gene. This is identical to previously described human family renal-coloboma syndrome [Sanyanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, (1995) Hum. Mol. Genet. 4, 2183-2184]. Heterozygous mutant mice exhibit defects kidney, optic nerve, and retinal layer of eye, homozygous embryos, development metanephric ventral regions inner ear severely affected. In addition, we observe deletion...
Loss-of-function mutations in the parkin gene (PARK2) and PINK1 (PARK6) are associated with autosomal recessive parkinsonism. deficiency was recently linked to mitochondrial pathology human cells Drosophila melanogaster, which can be rescued by parkin, suggesting that both genes play a role maintaining integrity. Here we demonstrate an acute down-regulation of SH-SY5Y severely affects morphology function, phenotype comparable induced deficiency. Alterations ATP production caused either or...
Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and mitochondria of mammalian cells. Thioredoxins (Txn), main substrates thioredoxin reductases (Txnrd), involved numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, apoptosis. To investigate individual contribution mitochondrial (Txnrd2) cytoplasmic (Txnrd1) vivo, we generated a mouse strain with conditionally targeted deletion Txnrd1. We show here that...
Aging is a major risk factor for large number of disorders and functional impairments. Therapeutic targeting the aging process may therefore represent an innovative strategy in quest novel broadly effective treatments against age-related diseases. The recent report lifespan extension mice treated with FDA-approved mTOR inhibitor rapamycin represented first demonstration pharmacological maximal mammals. Longevity effects may, however, be due to rapamycin’s on specific life-limiting...