K. C. Kent Lloyd
A5059847851- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Neuropeptides and Animal Physiology
- Reproductive Biology and Fertility
- Pluripotent Stem Cells Research
- Neuroendocrine Tumor Research Advances
- Animal testing and alternatives
- Adipose Tissue and Metabolism
- Helicobacter pylori-related gastroenterology studies
- RNA and protein synthesis mechanisms
- Sperm and Testicular Function
- Gastroesophageal reflux and treatments
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Diet and metabolism studies
- bioluminescence and chemiluminescence research
- Metabolomics and Mass Spectrometry Studies
- Veterinary Equine Medical Research
- Biomedical Text Mining and Ontologies
- Genetics, Aging, and Longevity in Model Organisms
- Gastrointestinal motility and disorders
- Bioinformatics and Genomic Networks
- Cell Image Analysis Techniques
University of California, Davis
2016-2025
National Hospital
2025
George Washington University
2025
U-M Rogel Cancer Center
2024
Universidad Nacional
2022
Helmholtz Zentrum München
2017
German Center for Neurodegenerative Diseases
2017
Technical University of Munich
2017
Munich Cluster for Systems Neurology
2017
Charité - Universitätsmedizin Berlin
2016
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...
In 2007, the International Knockout Mouse Consortium (IKMC) made ambitious promise to generate mutations in virtually every protein-coding gene of mouse genome a concerted worldwide action. Now, 5 years later, IKMC members have developed high-throughput trapping and, particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones 1,700 strains, most them conditional. A common web portal (www.knockoutmouse.org) has been established, allowing...
Abstract The role of sex in biomedical studies has often been overlooked, despite evidence sexually dimorphic effects some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, found a large proportion mammalian traits both mutants are influenced by sex. This result implications interpreting disease phenotypes animal models humans.
Abstract The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of metabolome and changes during diseases or aging remain poorly understood. Here, we generate a atlas wildtype mouse from 10 anatomical regions spanning adolescence old age. We combine data three assays structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between age groups, but not by sex. A shift in sphingolipid patterns related myelin remodeling is...
Topologically associating domain (TAD) boundaries partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotypes1-3, but overall extent to which this occurs remains unknown. Here we demonstrate targeted deletions of TAD a range disruptions in vivo function organismal development. We used CRISPR editing mice individually delete eight (11-80 kb size) from genome. All examined...
Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), physiological role of active transport its regulation. Hence we measured contents, osmolality, Glc, Na+, K+ normally feeding rats, rabbits, dogs. Measured were compatible with portion not accounted by Na+ salts, amino acids, peptides. Mean...
Neuregulin-1 (NRG1) and its ErbB2/B4 receptors are encoded by candidate susceptibility genes for schizophrenia, yet the essential functions of NRG1 signaling in CNS still unclear. Using CRE/LOX technology, we have inactivated ErbB2/B4-mediated specifically CNS. In contrast to expectations, cell layers cerebral cortex, hippocampus, cerebellum develop normally mutant mice. Instead, loss impairs dendritic spine maturation perturbs interactions postsynaptic scaffold proteins with glutamate...
Coordinated regulation of neuronal progenitor differentiation in the subventricular zone (SVZ) is a fundamental feature adult neurogenesis. However, molecular control this process remains mostly undeciphered. Here, we investigate role neuregulins (NRGs) and show that NRG receptor, ErbB4, primarily expressed by polysialylated neural cell adhesion molecule immature neuroblasts but also detected subset GFAP + astroglial cells, ependymal Dlx2 precursors SVZ. Of ligands, both NRG1 -2 are NRG2...
Embryonic stem cells (ESCs) and induced pluripotent (iPSCs) efficiently generate all embryonic cell lineages but rarely extraembryonic types. We found that microRNA miR-34a deficiency expands the developmental potential of mouse cells, yielding both strongly inducing MuERV-L (MERVL) endogenous retroviruses, similar to what is seen with features totipotent two-cell blastomeres. restricts acquisition expanded fate in it represses MERVL expression through transcriptional regulation, at least...
Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis biogenesis iron-sulfur clusters. To determine the biological function FDXR, we generated Fdxr-deficient mouse model found that loss Fdxr led to embryonic lethality potentially due iron overload in developing embryos. Interestingly, mice heterozygous had short life span were prone spontaneous tumors liver abnormalities, including steatosis, hepatitis, hepatocellular carcinoma....
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study evolution, mechanisms of drug response and resistance, tailoring chemotherapeutic approaches for individual patients. The lack robust standards reporting on PDX has hampered the ability researchers find relevant associated data. Here we present minimal information standard (PDX-MI) generation, quality assurance, use models. PDX-MI defines describing clinical attributes a...
Abstract The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and phenotyping knockout mouse line for every protein-coding gene. To date, the IMPC has generated characterised 5186 mutant lines. One-third lines have been found to be non-viable over 300 new models human disease identified thus far. While current bioinformatics efforts are focused on translating results better understand processes, data also aids understanding...
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures how essential gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice the International Mouse Phenotyping Consortium essentiality carried out human cell lines. We propose cross-species classification across Full Spectrum Intolerance Loss-of-function (FUSIL)...
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...