A5039809554- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Single-cell and spatial transcriptomics
- Digestive system and related health
- Immune Cell Function and Interaction
- Trace Elements in Health
- Genetics, Aging, and Longevity in Model Organisms
- Diet, Metabolism, and Disease
- Ubiquitin and proteasome pathways
- Transgenic Plants and Applications
- Escherichia coli research studies
- Diabetes and associated disorders
- Galectins and Cancer Biology
- Clinical Nutrition and Gastroenterology
- Immune cells in cancer
- Cancer-related gene regulation
- Neurogenetic and Muscular Disorders Research
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Skin and Cellular Biology Research
- Viral gastroenteritis research and epidemiology
- Wnt/β-catenin signaling in development and cancer
- Pancreatic function and diabetes
The University of Texas Southwestern Medical Center
2015-2023
Southwestern Medical Center
2020-2023
Oregon Health & Science University
2019
With the wide availability of massively parallel sequencing technologies, genetic mapping has become rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification N-ethyl-N-nitrosourea-induced mutations that cause phenotypes mice. All are identified by whole exome G1 progenitor and their zygosity is established G2/G3 mice before phenotypic assessment. Quantitative qualitative traits, including lethal effects, single or multiple combined pedigrees...
Significance The present study used a forward genetic approach to identify new causative mutations in an environmentally sensitized screen for colitis. A candidate mutation Gatm , verified by CRISPR/Cas9 targeting, demonstrated the need rapid replenishment of cytoplasmic ATP within colonic epithelial cells restore barrier integrity. This specified requirement energy avert colitis suggests category with potential cause inflammatory bowel disease.
Precise control of Wnt signaling is necessary for immune system development. In this study, we detected severely impaired development all lymphoid lineages in mice, resulting from an N-ethyl-N-nitrosourea-induced mutation the limb region 1-like gene (Lmbr1l), which encodes a membrane-spanning protein with no previously described function immunity. The interaction LMBR1L glycoprotein 78 (GP78) and ubiquitin-associated domain-containing 2 (UBAC2) attenuated lymphocytes by preventing maturation...
Significance Activation of Toll-like receptors by microbes or host-derived molecules triggers signaling that promotes inflammation and may contribute to the development autoimmunity. Here we show excessive innate immune (TLRs) TLR3, TLR7, TLR9 is causative for inflammatory disease in mice with mutations Smcr8 . The cellular mechanism their hyperactivation likely prolonged ligand–receptor contact lysosomes phagosomes, trafficking which regulated SMCR8-WDR41-C9ORF72 complex cells. We also...
Significance IBD is one of the most common early manifestations LRBA deficiency and has been attributed to impaired regulatory T cell function. However, whether other immune types also contribute not comprehensively tested. We found that, in LRBA-deficient mice, DCs significantly colitis DSS model. showed that blocking innate signaling from endosomal TLRs, TLR3, TLR7, TLR9, Lrba −/− mice dramatically reduced their susceptibility DSS-induced colitis. Our data indicate a role for limiting TLR...
Abstract A key feature in intestinal immunity is the dynamic barrier, which separates host from resident and pathogenic microbiota through a mucus gel impregnated with antimicrobial peptides. Using forward genetic screen, we have found mutation Tvp23b , conferred susceptibility to chemically induced infectious colitis. Trans-Golgi apparatus membrane protein TVP23 homolog B (TVP23B) transmembrane conserved yeast humans. We that TVP23B controls homeostasis of Paneth cells function goblet...
Prkd2-dependent phosphorylation of Bcl6 inhibits T FH cell differentiation.
In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for aberrant immune function, we identified with syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid myeloid hypoplasia together diminished T cell-independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), oxidoreductase that functions nascent folding the endoplasmic reticulum. deficiency...
Significance We developed software called Candidate Explorer (CE) that uses a machine-learning algorithm to identify chemically induced mutations are causative of screened phenotypes. CE determines the probability mutation will be verified as for phenotype if gene is independently targeted knockout or recreation mutation. 67 parameters from mapping data—including gene, mutation, genotype, allelism, and information—to determine Score verification probability. used evaluate ∼87,000...
ABSTRACT Myosin ID (MYO1D) is a member of the class I myosin family. We screened 48,649 third generation (G3) germline mutant mice derived from N-ethyl-N-nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration dextran sodium sulfate (DSS). found and validated mutations in Myo1d as cause increased susceptibility to DSS-induced colitis. MYO1D produced epithelium, colitis phenotype dependent on nonhematopoietic compartment mouse. Moreover, appears...
ABSTRACT Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) transcription factor family. ARNT2 heterodimerizes with several members family, including single-minded homolog-1 (SIM1) and neuronal PAS domain protein 4 (NPAS4), primarily in neurons central nervous system. We screened 64,424 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea (ENU)-mutagenized great-grandsires for weight abnormalities....