Lillian Garrett
A5081236821- RNA Research and Splicing
- RNA modifications and cancer
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Connexins and lens biology
- Adipose Tissue and Metabolism
- Circadian rhythm and melatonin
- Genomics and Rare Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Effects of Radiation Exposure
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolism and Genetic Disorders
- Thyroid Disorders and Treatments
- CRISPR and Genetic Engineering
- Biochemical Analysis and Sensing Techniques
Helmholtz Zentrum München
2015-2024
Ludwig-Maximilians-Universität München
2023
Utrecht University
2021
Maastricht University
2011
University College Cork
2008-2010
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...
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...
Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding the enzymes catalyzing these modifications, their substrates and functions, remains vague. Amongst RNA N 6 -methyladenosine (m A) is widespread found in messenger (mRNA), ribosomal (rRNA), noncoding RNAs. Here, we undertook a systematic screen to uncover new methyltransferases. We demonstrate that methyltransferase-like 5 (METTL5) protein catalyzes m A 18S rRNA at...
Translation of the expanded (ggggcc)n repeat in C9orf72 patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA inclusions. To elucidate their role pathogenesis, we generated transgenic mice expressing codon-modified (GA)149 conjugated cyan fluorescent protein (CFP). Transgenic progressively developed inclusions predominantly motoneurons interneurons spinal cord brain stem deep cerebellar nuclei. Poly-GA co-aggregated p62, Rad23b newly...
Genome-wide association studies (GWAS) identified the MEIS1 locus for Restless Legs Syndrome (RLS), but causal single nucleotide polymorphisms (SNPs) and their functional relevance remain unknown. This contains a large number of highly conserved noncoding regions (HCNRs) potentially functioning as cis -regulatory modules. We analyzed these HCNRs allele-dependent enhancer activity in zebrafish mice found that risk allele lead SNP rs12469063 reduces Meis1 expression domain murine embryonic...
Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease naturally limits these animals. We compare more than 200 phenotypes over 20 tissues aged animals fed lifelong or ad libitum access food diet determine whether molecular, cellular, physiological and histopathological aging features develop slowly controls. also analyze the effects on...
Clinical presentation of congenital heart disease is heterogeneous, making identification the disease-causing genes and their genetic pathways mechanisms action challenging. By using in vivo electrocardiography, transthoracic echocardiography microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural functional cardiac abnormalities, here we identify 705 with arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these genes, 486 have not been...
Circular RNAs (circRNAs) are a large class of noncoding RNAs. Despite the identification thousands circular transcripts, biological significance most them remains unexplored, partly because lack effective methods for generating loss-of-function animal models. In this study, we focused on circTulp4, an abundant circRNA derived from Tulp4 gene that is enriched in brain and synaptic compartments. By creating circTulp4-deficient mouse model, which mutated splice acceptor site responsible...
ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading amino acid substitutions the encoded proteins, is mainly expressed brain. Of all ADAR2-mediated edits, a single one pre-mRNA of AMPA receptor subunit GluA2 essential for survival. Hence, early postnatal death mice lacking ADAR2 averted when critical edit engineered into both encoding Gria2 alleles. Adar2−/−/Gria2R/R display normal appearance and life span, but general phenotypic...
Abstract Neonatal maternal separation has been widely used to model the well‐established causal relationship between stress in early life and later development of depression. As corticotrophin‐releasing factor (CRF) vasopressin (AVP) have implicated depression, we aimed determine long‐term effects on these neuropeptide systems, also explore whether are gender‐dependent. Immunohistochemical staining CRF, AVP c‐Fos was assess systems were affected following an acute swim male female maternally...
Genetically modified mouse models have proven useful to study learning and memory processes the neurocircuitry molecular mechanisms involved, as well develop therapies for diseases involving cognitive impairment. A variety of tests been developed measure cognition in mice, here we present those established regularly used German Mouse Clinic. The test paradigms carefully chosen according reliability results disease relevance functions assessed. Further criteria were time efficiency ease...
Stress and an altered stress response have been associated with many multifactorial diseases, such as psychiatric disorders or neurodegenerative diseases. As currently mouse mutants for each single gene are generated phenotyped in a large-scale manner, it seems advisable also to test these alterations their responses. Here we present the determinants of robust reliable non-invasive stress-responsivity mice. is applied through restraining mice tubes recording behavior Open Field 20 min after...
Animal welfare requires the adequate housing of animals to ensure health and well-being. The application environmental enrichment is a way improve well-being laboratory animals. However, it important know whether these items can be incorporated in experimental mouse husbandry without creating divide between past future results. Previous small-scale studies have been inconsistent throughout literature, not yet completely understood how might endanger comparability results scientific...
Abstract Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed characterize so-far unannotated mammalian genes. Here, we generate analyze phenotypic data of 2016 knockout mouse strains under aegis International Mouse Phenotyping Consortium (IMPC) find 974 gene knockouts with strong phenotypes. 429 those had no previous link metabolism 51 genes functionally...
Abstract Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for can be limited value because it may restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds markers in male C57BL/6J mice. For each phenotype, establish lifetime profiles determine when age-dependent change is first detectable relative young adult baseline. We examine key...
Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is lack of specific treatments only few hundred the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables mass identification potential candidates that mutated form could trigger but often not confirmed be causal. Knockout (KO) mouse models essential understand causality genes by allowing highly standardized...
Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role Irp2 regulating metabolism. While both show that loss results microcytic anemia and altered body distribution, discrepant drawn into question brain One model shows aged deficient mice develop adult-onset progressive neurodegeneration associated with axonal degeneration Purkinje cells nervous system. These...
Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, premature death. Here, to more thoroughly investigate manifestations of JNCL mutation, we performed a broad phenotyping study mice. Homozygous mice, congenic on C57BL/6N background, displayed subtle deficits in sensory tasks at 10–14 weeks age. also electroretinographic changes reflecting cone...
Abstract Background The role played by adult neurogenesis in anxiety is not clear. A recent study revealed a surprising positive correlation between increased and elevated following chronic voluntary wheel running multiple behavioural testing mice, suggesting that hippocampal involved the genesis of anxiety. To exclude possible confounding effect may have occurred aforementioned study, we assessed (1) effects mouse (14 vs. 28 days) on just one test; open field, (2), using different markers,...
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum dietary donor can increase risk for mental health issues neurological disorders offspring, has not been explored whether paternal influences behavioral cognitive functions next generation. Here, we report elevated a mouse model, transiently applied prior to mating, resulted offspring animals...