Molecular Genetics Commons^™

Functional Characterization Of Rai1 In Zebrafish, Joshua S. Beach

Theses and Dissertations

Smith-Magenis Syndrome (SMS; OMIM #182290) is a multiple congenital abnormality and intellectual disability (ID) disorder caused by either an interstitial deletion of the 17p11.2 region containing the retinoic acid induced-1 (RAI1) gene or a mutation of the RAI1 gene. Individuals diagnosed with SMS typically present characteristics such as ID, self-injurious behavior, sleep disturbance, ocular and otolaryngological abnormalities, craniofacial and skeletal abnormalities, neurological and behavioral abnormalities, as well as other systemic defects and manifestations. Previous work by Vyas in 2009 showed temporal expression of rai1 in zebrafish embryos as early as 9 hpf. We hypothesize that there is maternal …

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …

Profile Of The Unfolded Protein Response In C. Elegans Depleted Of The Translational Chaperone, Nac., Caylin S. Murray

Masters Theses, 2010-2019

The function of a protein is a direct consequence of its final structure, which is achieved by protein-folding processes that generate a tertiary state through the juxtaposition of locally formed secondary structures. Because all cells need functional proteins to survive, each contains robust and redundant mechanisms that regulate the folding of newly forming proteins, and the refolding of misfolded proteins that are often generated during stress. Essential to these mechanisms, chaperones are proteins that aid in protein folding of nascent and misfolding protein without being incorporated in the final structure. One chaperone complex, the nascent polypeptide-associated complex (NAC), aids in …

In Vivo Identification Of Eugenol-Responsive And Muscone-Responsive Mouse Odorant Receptors, Timothy S. Mcclintock, Kaylin Adipietro, William B. Titlow, Patrick Breheny, Andreas Walz, Peter Mombaerts, Hiroaki Matsunami

Physiology Faculty Publications

Our understanding of mammalian olfactory coding has been impeded by the paucity of information about the odorant receptors (ORs) that respond to a given odorant ligand in awake, freely behaving animals. Identifying the ORs that respond in vivo to a given odorant ligand from among the ∼1100 ORs in mice is intrinsically challenging but critical for our understanding of olfactory coding at the periphery. Here, we report an in vivo assay that is based on a novel gene-targeted mouse strain, S100a5-tauGFP, in which a fluorescent reporter selectively marks olfactory sensory neurons that have been activated recently in vivo. Because each …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

Development Of A Molecular Gram-Stain Assay For The Diagnosis Of Blood Stream Infections Associated With Sepsis, Douglas Bryan Litwin

Dissertations and Theses (Open Access)

Sepsis is a serious medical condition resulting from the severe dysregulation of the immune response that is generally triggered by infection. It affects more than 1.1 million Americans, has an average mortality rate of 30%, and is estimated to cost $24.3 billion annually. Currently, blood culture followed by Gram-stain analysis is the gold standard for diagnosing bacterial infections associated with sepsis. This method generates a high rate of false negative results and, in general, requires 20 to 48 hr to provide results. Both of these problems are related to the requirement that the bacterial pathogens grow under defined laboratory conditions. …

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

Secretory Iga Is Concentrated In The Outer Layer Of Colonic Mucus Along With Gut Bacteria, Eric W. Rogier, Aubrey L. Frantz, Maria E. C. Bruno, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Antibodies of the secretory IgA (SIgA) class comprise the first line of antigen-specific immune defense, preventing access of commensal and pathogenic microorganisms and their secreted products into the body proper. In addition to preventing infection, SIgA shapes the composition of the gut microbiome. SIgA is transported across intestinal epithelial cells into gut secretions by the polymeric immunoglobulin receptor (pIgR). The epithelial surface is protected by a thick network of mucus, which is composed of a dense, sterile inner layer and a loose outer layer that is colonized by commensal bacteria. Immunofluorescence microscopy of mouse and human colon tissues demonstrated that …

Cd21 And Cd24 Co-Expression: A Translational Model Between Mouse And Human, Abigail Benitez

Loma Linda University Electronic Theses, Dissertations & Projects

Systemic Lupus Erythematosus and Rheumatoid Arthritis are B cell-mediated autoimmune diseases that afflict millions of people worldwide. B cell-targeted therapies for these diseases result in variable clinical outcomes. Thus, a need exists to better understand the dynamics of human B cell production and function. The mouse model has provided a foundation for understanding the mechanisms involved in human B cell development and autoimmune disease. However, differences in mouse and human B cells are not fully understood. Our work shows that the co-expression of CD21 and CD24, determined by 7-color flow cytometry, can be used to demarcate developmental subsets of B …

The Development Of A Comprehensive Antifungal Susceptibility Testing Assay For Vulvovaginal Candidiasis Therapy, David Hardaker

Graduate School of Biomedical Sciences Theses and Dissertations

Vulvovaginal candidiasis is the most common fungal infection of the female urogenital tract, commonly caused by Candida albicans and C. glabrata. However, treatment can be difficult when caused by non-albicans strains due to resistance to the oral antifungal drug fluconazole. The mechanism through which strains of Candida, particularly C. glabrata, develop resistance to different antifungal classes has not been completely characterized. The ergosterol biosynthesis pathway, an important component of the cell membrane, is the major target of antifungals such as fluconazole, an inhibitor of the ERG 11 gene. Current research shows that an upregulation of specific genes in C. glabrata …

Modulated Functions Of The Fanconi Anemia Core Complex, Yaling Huang

Dissertations and Theses (Open Access)

Cells derived from Fanconi anemia (FA) patients are characterized by hypersensitivity to DNA interstrand crosslinks (ICLs), suggesting that FA genes play a role in ICL repair. Fanconi anemia core complex (including A, B, C, E, F, G, L, FAAP20, and FAAP100) activates the Fanconi pathway by providing the essential E3 ligase activity for FANCD2 mono-ubiquitination. Previous studies suggested the existence of three protein-protein interaction groups. However, the functions of most FA core complex protein are still limited to their presence in the complex. How the spatially-defined FANCD2 ubiquitination is accomplished by the core complex remains unknown.

To elucidate the roles …

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, [email protected] K. Busiek

Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …

Structural And Functional Analysis Of Harv1 Lipid Binding, Jamie Francisco

Graduate School of Biomedical Sciences Theses and Dissertations

Cardiovascular disease (CVD) has the highest mortality rate worldwide and is considered epidemic in the United States. Statins as the primary and almost sole method of treatment for cholesterol-related CVD, but they have limitations. Proper sterol transport is needed to maintain normal blood lipid levels. Studies have shown that misregulation of lipid trafficking aids in the progression of CVD and in the activation of the unfolded protein response (UPR). Misregulation of lipid and sterol homeostasis also results in the loss of lipid rafts, known cellular signaling hubs and major components of ER associated membrane contact sites. Arv1 is a highly …

B Cell Tolerance In Health And Disease, Murali Gururajan, Vishal J. Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids …

Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske

Center for Molecular Medicine and Genetics

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and …

The Role Of Angiotensinogen In Atherosclerosis And Obesity, Congqing Wu

Theses and Dissertations--Nutritional Sciences

Angiotensinogen is the only known precursor in the renin-angiotensin system, a hormonal system best known as an essential regulator of blood pressure and fluid homeostasis. Angiotensinogen is sequentially cleaved by renin and angiotensin- converting enzyme to generate angiotensin II. As the major effector peptide, angiotensin II mainly function through angiotensin type 1 receptor.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and more recently renin inhibitors are widely known as the 3 classic renin-angiotensin system inhibitory drugs against hypertension and atherosclerosis. Here, we developed an array of regents to explore the effects of angiotensinogen inhibition. First, we demonstrated that genetic deficiency of …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

C-Rel Is A Transcriptional Target Of Mesoderm Inducer In Xenopus Like 1 (Mixl1), Aaron C. Raymond

Dissertations and Theses (Open Access)

MIXL1, an evolutionarily conserved, paired-type homeobox transcription factor induced by BMP4/TGFb signaling, is a critical regulator of embryonic and adult hematopoiesis. Several lines of evidence implicate MIXL1 in hematopoietic transformation: (i) Aberrant MIXL1 expression is seen in human CML ( Chronic Myelogenous Leukemia) in blast crisis, AML (Acute myelogenous leukemia), B cell lymphomas and pediatric ALL (Acute lymphocytic leukemia). (ii) Retroviral transduction of Mixl1 induces AML in murine models. Nonetheless, mechanisms underlying MIXL1 mediated proliferative, survival advantages are unknown.

The goal of my studies is to understand if and how aberrant MIXL1 expression contributes to leukemogenesis. As a first step, …

A Process Similar To Autophagy Is Associated With Cytocidal Chloroquine Resistance In Plasmodium Falciparum, David Gaviria, Michelle F. Paguio, Lindsey B. Turnbull, Asako Tan, Amila Siriwardana, Debasish Ghosh, Michael T. Ferdig, Anthony P. Sinai, Paul D. Roepe

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP) primary structures interact with distinct prion conformations to influence pathogenesis, …

Fecal Transplantation Does Not Transfer Either Susceptibility Or Resistance To Food Borne Listeriosis In C57bl/6 And Balb/C/By Mice, Tanya Myers-Morales, Kate M. Bussell, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The composition of the intestinal microbiota has wide reaching effects on the health of an individual, including the development of protective innate immune responses. In this report, a fecal transplantation approach was used to determine whether resistance to food borne listeriosis was dependent on the murine gut microbiota. Transplantation of BALB/c/By feces did not increase the susceptibility of C57BL/6 mice to Listeria monocytogenes infection. Likewise, transplantation of C57BL/6 fecal matter did not enhance the resistance of BALB/c/By mice. Thus, intestinal microbiota composition is not a key factor that confers either susceptibility or resistance to food borne listeriosis in mice.

Med13p Prevents Stress-Independent Mitochondrial Hyperfragmentation And Aberrant Apoptosis Activation In Saccharomyces Cerevisiae By Controlling Cyclin C Nuclear Localization, Svetlana Khakhina

Graduate School of Biomedical Sciences Theses and Dissertations

During aging, and as a result of environmental changes, cells are exposed to elevated levels of reactive oxygen species (ROS). High ROS levels induce lipid oxidation, protein aggregation, mitochondrial hyperfragmentation, DNA damage and programmed cell death (PCD), also called apoptosis. PCD is a highly regulated process and its misregulation has been linked to neurodegenerative diseases and cancer development.

Our hypothesis is that cyclin C plays a role in the initiation of apoptosis. During normal conditions, cyclin C represses the transcription of stress response genes (SRG). In response to stress, cyclin C translocates to the cytoplasm where it facilitates mitochondrial hyperfragmentation …

Prkca: Identification Of A Novel Downstream Target Of Wt1, Devin Jones

Dissertations and Theses (Open Access)

Wilms tumor is a childhood tumor of the kidney arising from the undifferentiated metanephric mesenchyme. Tumorigenesis is attributed to a number of genetic and epigenetic alterations. In 20% of Wilms tumors, Wilms tumor gene 1 (WT1) undergoes inactivating homozygous mutations causing loss of function of the zinc finger transcription factor it encodes. It is hypothesized that mutations in WT1 result in dysregulation of downstream target genes, leading to aberrant kidney development and/or Wilms tumor. These downstream target genes are largely unknown, and identification is important for further understanding Wilms tumor development. Heatmap data of human Wilms tumor protein …

Apolipoprotein E Mediates Attachment Of Clinical Hepatitis C Virus To Hepatocytes By Binding To Cell Surface Heparan Sulfate Proteoglycan Receptors, Jieyun Jiang, Xianfang Wu, Hengli Tang, Guangxiang Luo

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglycans (HSPGs). In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b (HCV1b) obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells (DHHs). DHHs were found to resemble primary …

Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer. HPV 16 E6, one of two viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several apoptotic proteins, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV+ cells to apoptosis. To test this prediction, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding, and identified several candidates from different chemical classes. Testing hits for dose-dependency and specificity in vitro and for toxicity …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …