Life Sciences Commons^™

Lifecycle Efficiency Of Mice Divergently Selected For Heat Loss, Adrienne Bhatnagar

Department of Animal Science: Dissertations, Theses, and Student Research

Divergent selection for heat loss as an indication of maintenance energy requirements in mice resulted in a low (ML) and high maintenance line (MH), and an intermediate control line (MC). Improved feed efficiency has been observed in ML mice, which would be economically beneficial in livestock species. However, previous work showed evidence of unfavorable correlated responses to selection in ML mice compared to MH mice. Therefore, the objective of this study was to model a lifecycle similar to a livestock production system using these lines and determine if these correlated responses diminish the benefit of improved feed efficiency by calculating …

Researching The Effects Of Osteoarthritis As A Systemic Immune Response, Danielle Peterson, Dr. David Kooyman

Journal of Undergraduate Research

Our bodies are dynamic structures that do not operate as individual compartments, but as a whole. When something goes awry in one specific tissue or organ, specific signals from that diseased area are released affect other tissues. I received an ORCA grant last year to study my hypothesis that degradation of Osteoarthritis (OA) is primarily associated with a systemic immune response to trauma of articular cartilage. In order to verify this hypothesis, a treatment that creates OA in one localized area while other tissues remained undamaged was needed. The OA genetic mutant mice that researchers normally turn to couldn’t be …

The Wnt/Planar Cell Polarity Pathway Component Vangl2 Induces Synapse Formation Through Direct Control Of N-Cadherin, Tadahiro Nagaoka, Riuko Ohashi, Ayumu Inutsuka, Seiko Sakai, Nobuyoshi Fujisawa, Minesuke Yokoyama, Yina H. Huang, Michihiro Igarashi, Masashi Kishi

Dartmouth Scholarship

Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic …

Independent Murine Biosynthesis Of Threonine: Expression Of A Complete Bacterial Biosynthetic Pathway In Mice, Ryan D. Mcallister, Dr. David Kooyman

Journal of Undergraduate Research

Threonine is one of the 20 common amino acids found in nature. It is a limiting factor for the growth of many non-ruminant animals such as swine and mice and must be obtained from their diet. When threonine is absent from the diet of these animals, the other amino acids present cannot be fully utilized. The result is poor conversion of plant to animal protein (1). We proposed producing transgenic mice using the genes from the known five-step bacterial pathway for threonine synthesis (2). The introduction of these bacterial pathways to mice would eliminate the need for dietary supplementation of …

Mapping Of The Immune Response Gene(S) Controlling Susceptibility To Murine Experimental Orchitis, Randall Roper

Journal of Undergraduate Research

The research project I proposed entailed mapping the gene or genes that control susceptibility to Murine Experimental Orchitis by using a large backcross population of 110 animals. These animals have been generated by obtaining an Fl population from the susceptible SJL mice and resistant B lO.S mice and crossing the susceptible Fl population with disease resistant BlO.S mice. Through the use of a histological report of the susceptibility of the large backcross population to Experimental Allergic Orchitis, and the use of microsatellite and RAPD markers to identify distinguishing polymorphisms, the gene may be linked to a specific chromosome of the …

Producing A Transgenic Mouse, Michael Hatch, Dr. David Kooyman

Journal of Undergraduate Research

One of the greatest challenges in the world today is providing adequate nutrition for all, particularly in third world nations. One potential way to improve worldwide nutrition is to use transgenic animals to create a better livestock base. Transgenic animals can potentially be bigger, stronger, and better producers of meat and milk than their non-transgenic counterparts. The purpose of this research project was to produce transgenic mice, serving as a model for what could potentially occur with larger mammals with more agricultural value, such as cows or pigs.

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

Circadian Regulation Of Mtor Signaling Via Bmal1 Dependent Mechanism, Rohini Vishal Khapre

ETD Archive

Understanding mechanisms of aging is important for the treatment and prevention of age-associated pathologies. However, these mechanisms are not well understood. Recently we have demonstrated that the circadian clock (an internal time keeping system) regulates longevity in mammals, but the molecular mechanisms are not known. The aim of our current study is to investigate a possible interconnection between the circadian clock and mTORC1 (mammalian target of Rapamycin) signaling pathway. mTORC1 pathway is a nutrient response pathway involved in many cellular processes many recent studies indicate a role of mTORC1 pathway in aging. Here we demonstrate that circadian system regulates mTORC1 …

Non-Invasive Mri And Spectroscopy Of Mdx Mice Reveal Temporal Changes In Dystrophic Muscle Imaging And In Energy Deficits., Christopher R. Heier, Alfredo D. Guerron, Alexandru Korotcov, Stephen Lin, Heather Gordish-Dressman, Stanley Fricke, Raymond W. Sze, Eric P. Hoffman, Paul Wang, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging …

The Role Of Progestogen Neurosteroids In Behaviors Relevant For Autism Spectrum Disorders, Danielle Christine Llaneza

Legacy Theses & Dissertations (2009 - 2024)

Autism spectrum disorder (ASD) affects children across the U.S. and is characterized by deficits in social communication and restrictive/repetitive behaviors, for which few therapeutic interventions have been successful. Steroid hormones, such as progesterone (P4) and its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), can exert neuroprotective effects, influence synaptic morphology, mediate behavioral outcomes, and influence stress-responding. In this thesis, the behaviors and baseline levels of the stress hormone, corticosterone, P4, and 3α,5α-THP are investigated in BTBR T+ Itpr3tf/J (BTBR) mice, a proposed ASD model. It was hypothesized that BTBR mice would show abnormalities in behaviors and in levels of steroids and neuroendocrine factors. Results …

Mouse Salivary Gland Development Requires Optimal Substrate Compliance, Sarah Beth Peters

Legacy Theses & Dissertations (2009 - 2024)

The embryonic mouse submandibular salivary gland (mSMG) is a classic model to study mechanochemical signals involved in morphogenesis and differentiation amongst multiple, interacting cell populations. Scaffold compliance is alters cellular phenotype, but little is known about the effects of compliance on organogenesis. The overall aim of this project was to demonstrate that the processes of salivary gland epithelial branching morphogenesis and differentiation require a compliant, in vivo-like environment and are disrupted outside of this range.

Effect Of Folate Deficiency On Mtor Signaling Network On The Liver Of Wild Type Mice, Essra Moussawi

Wayne State University Theses

Through various studies of dietary nutrients on the affects of the physiological and molecular pathways are a key study in understanding the interaction between dietary nutrients and the human genome that may severely impact the development of various cancers. A primary approach is observing the dietary nutrients, that we consume and how it plays a role in the cellular pathway of our bodies through experimental methods. Folate deficiency (FD) has shown, through studies, to play a role anti-cancer progression. Our goal was to observe the autophagy related proteins in the mTOR signaling pathway as it was suggested that mTOR may …

High Fat Diet Increased Serum Glutamate Dehydrogenase More Than Chronic Acetaminophen Dosing In Female Mice, Elizabeth Ruth Behmer

All Graduate Theses, Dissertations, and Other Capstone Projects

This laboratory study examined the effects of acetaminophen overdose in normal fed and high-fat fed female mice. Forty female mice were placed on normal and high-fat diets at 4 weeks old. When the mice were significantly different in weight (between 6 and 9 months old), half the mice were dosed with acetaminophen. These mice were daily given an overdose of acetaminophen for 14 days. The dose used was 300 mg/kg mouse (LD50 = 338 mg/kg). The control group was given 10 µl water/g mouse. Levels of serum glutamate dehydrogenase (GDH) were measured to indicate liver damage. GDH is released from …

Inflammatory Cytokine Gene Expression In Mesenteric Adipose Tissue During Acute Experimental Colitis, William Conan Mustain, Marlene E. Starr, Joseph Daniel Valentino, Donald A. Cohen, Daiki Okamura, Chi Wang, B. Mark Evers, Hiroshi Saito

Markey Cancer Center Faculty Publications

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

METHODS: Experimental colitis was induced in 6-month-old C57BL/6 …

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

Use Of Irf-3 And/Or Irf-7 Knockout Mice To Study Viral Pathogenesis: Lessons From A Murine Retrovirus-Induced Aids Model, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Interferon regulatory factor (IRF) regulation of the type I interferon response has not been extensively explored in murine retroviral infections. IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant to LP-BM5-induced pathogenesis. However, further analyses strongly suggested that resistance could be attributed to strain 129-specific contamination of the known retrovirus resistance gene Fv1. Therefore, caution should be taken when interpreting phenotypes observed in these knockout mice, as strain 129-derived genetic polymorphisms may explain observed differences.

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 …

Adam17-Mediated Processing Of Tnf-Α Expressed By Antiviral Effector Cd8+ T Cells Is Required For Severe T-Cell-Mediated Lung Injury, Matthew P. Deberge, Kenneth H. Ely, Guang-Shing Cheng, Richard I. Enelow

Dartmouth Scholarship

Influenza infection in humans evokes a potent CD8+ T-cell response, which is important for clearance of the virus but may also exacerbate pulmonary pathology. We have previously shown in mice that CD8+ T-cell expression of TNF-a is required for severe and lethal lung injury following recognition of an influenza antigen expressed by alveolar epithelial cells. Since TNF-a is first expressed as a transmembrane protein that is then proteolytically processed to release a soluble form, we sought to characterize the role of TNF-a processing in CD8+ T-cell-mediated injury. In this study we observed that inhibition of ADAM17-mediated processing of TNF-a by …

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, …

Degeneration Of Articular Cartilage In The Temporomandibluar Joint Of Mice With Disproportionate Micromelia (Dmm), Robert R. Seegmiller

Journal of Undergraduate Research

Osteoarthritis is a common degenerative joint disease affecting humans today. This disease leads to premature degradation of articular cartilage in joints, such as the knee, and it can be caused by mutations in collagen coding genes. Collagen is the basic building block of cartilage, so any mutations would affect the response of collagen to outside factors.

Type Iia Procollagen – Osteoarthritis Biomarker In Dmm Mice, John Mcallister, Kenneth Merrell, Dr. Robert E. Seegmiller

Journal of Undergraduate Research

Arthritis is a painful, debilitating disease that affects sixty-six million Americans (The Arthritis Foundation 2005). Osteoarthritis (OA), results in joint degeneration caused by cartilage erosion and synovial inflammation. While the causes of OA remain unclear, current evidence suggests that both mechanical and biochemical factors can initiate OA. Ethical and practical issues limiting the availability of human tissue in OA research necessitate the use of animal models. Mice with the disproportionate micromelia mutation (Dmm) exhibit histological characteristics similar to those of humans with OA. Use of Dmm as a model of OA may lead a discovery of a common mechanism associated …

Hormonal Effects On Antibody-Secreting Cell Migration, Brad Hyatt, Dr. Eric Wilson

Journal of Undergraduate Research

I started by following the injection protocol established by Weisz-Carrington , et al., administering 5 mg of progesterone and 4 µg of estrogen daily for 21 days, followed by 7 days of 2 mg of prolactin. Since progesterone and estrogen are lipid-soluble, olive oil was used as a solvent; unfortunately, even with heat and time, the lipid solvent never fully dissolved the hormones that we bought in powder form. Consequently, I was injecting more of a suspension than a solution, and I was never sure that all the hormone was delivered, or how much had been delivered in a form …

Retinal Detachment In Mice With Disproportionate Micromelia, Jared R. Jackson, Dr. Robert Seegmiller

Journal of Undergraduate Research

Stickler syndrome, caused by a mutation of the Collagen 2A1 gene, is the most common cause of inherited retinal detachment in children. A mutation of the same gene in mice causes Disproportionate Micromelia (Dmm). “In cases where mouse mutations occur in genes that are also responsible for human disorders, the mouse strains provide essential model systems for studies of pathogenetic mechanisms.” The purpose of this study is to find and document evidence of retinal detachment that is hypothesized in heterozygous (Dmm/+) mutant mice.

The Role Of Wnt Ligands In The Development Of Limb Musculature, Jordan Huber, Dr. Jeffery Barrow

Journal of Undergraduate Research

The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. By making a conditional allele of the O-acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and a tissue specific enhancer to drive Cre expression, we are able to eliminate the secretion of all Wnt ligands in tissues of interest. We eliminated the secretion of …

Effects Of Tlr-4 Blockers On The Severity Of Oa In Rage Knockout Mice, Jeffrey Kartchner, Dr. David Kooyman

Journal of Undergraduate Research

As the population in the US continues to age, osteoarthritis (OA) is becoming a larger issue, currently effecting over 27 million people1. Presently, pharmaceutical options aim to lessen the effects of the disease, while no preventative treatment is currently available. Much of the current arthritis research is targeted at the effects of inflammation on the progression of OA. Our lab has shown in previous research that mice lacking the Receptor for Advanced Glycation End Products (RAGE) are protected from OA2. Other labs have shown the possibility of Toll-like receptor 4 (TLR-4) involvement in the progression of the disease as well3. …

Mice Show Decreased Muscle Strength Bearing A Targeted Inactivation Of Nbmp2, Alina Schmidt, Dr. Laura Bridgewater

Journal of Undergraduate Research

An important secreted growth factor, bone morphogenic protein 2 (Bmp2), is involved in mesoderm formation, heart development, neurogenesis, skeletal development, axis formation, and muscle development 1 and is a member of the TGF-β superfamily of proteins. Members of the TGF-β superfamily are commonly known as secreted growth factors but has recently been discovered in the nucleus, known as nuclear Bmp21. nBmp2 bypasses the secretory pathway by having an alternative start codon downstream of the signal peptide.

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac

Assessing Premature Arthritis In Sedc Mutant Mice, Shaela Avery, Dr. Robert Seegmiller

Journal of Undergraduate Research

A recently discovered collagen gene mutation, spondyloepiphiseal dysplasia congenita (sedc), is found on the Col2a1 gene in both mice and humans. The mouse mutation is molecularly similar to the human SEDC mutation, which causes premature osteoarthritis. Studies, such as this one, in mouse models provide a greater understanding of this recently discovered mutation and help in finding ways to prevent osteoarthritis in humans.

Histological And Ultrastructural Evidence Of Osteoarthritis In Mice Carrying A Semi-Dominant Mutation Of Col2a1, Victoria Ryder, Dr. Robert Seegmiller

Journal of Undergraduate Research

Mice heterozygous for the semi-dominant mutation disproportionate micromelia (Dmm) express mild chondrodysplasia by three weeks postnatally. This phenotype is attributed to a deletion of three contiguous nucleotides within the Col2A1 gene on mouse chromosome 15. The phenotype of Dmm/+ mice resembles that of human Stickler syndrome, which can be caused by mutations in the human COL2A1 gene.

Construction Of A Col11a1 Transgene And The Study Of The Col11a1 Mutation In Mice, Dana L. Murphy, Dr. Laura C. Bridgewater

Journal of Undergraduate Research

Collagen fibrils play an important role in proper skeletal development. Defective collagen can cause human skeletal disorders such as osteoarthritis that affects an estimated 20.7 million Americans. A particular mouse line, housed here at BYU, contains a mutation in the Col11a1 gene. This mutation results in defective type XI collagen, which is an important component of articular cartilage, and eventually leads to osteoarthritis (1).