Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 28 for “"knock-in mice"”.
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Characterization Of The Skeletal Phenotype In Idua-W392X Knock-In Mice: Bone Metabolism Biomarkers
… catalyzes the degradation of the two glycosaminoglycans (GAGs); heparin sulfate (HS) and demantan sulfate (DS). The accumulation of HS and DS makes MPS I progressive with inevitable degeneration of multiple organ systems. Accumulated excess of GAGs on the skeletal system causes dysostosis …
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Intra-Regional Differences in Cerebellar Vulnerability of Spinocerebellar Ataxia Type 1 Mice
Increasing evidence demonstrates distinct regional differences across the cerebellum, yet whether these differences contribute to selective vulnerability in cerebellar disease remains an open question. Spinocerebellar Ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused …
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Biomechanical and physiological investigations in the IBMPFD animal model
Inclusion body myopathy associated with Paget’s disease of bone and frontotemporal dementia (IBMPFD; OMIM 167320) is an autosomal dominant inherited multisystem disorder caused by mutations in the valosin-containing protein (VCP) gene. Knock-in mice expressing the common human p.R155H VCP mutation …
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Genetic Analysis of Adipose Lineage and Development
Adipose tissues protect t against traumatic and thermal insults, and regulate lifespan, reproduction and metabolism. The importance of forming the appropriate number of adipocytes is highlighted by the significant metabolic disturbances that accompany too few (lipodystrophy) or too many (obesity) …
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Contextual Insights into the Rett Syndrome Transcriptome
Mutations in MECP2 are responsible for Rett syndrome (RTT), a severe X-linked neurological disorder characterized by loss of developmental milestones, intellectual disability and motor impairments. However, molecular insight into how these mutations affect the neuronal transcriptiome, disrupt …
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Repressor of Estrogen Receptor Activity (REA) is a gene dose-dependent coregulator protein affecting estrogen signaling and cell survival
… (REA) is an evolutionarily conserved protein with established roles in multiple, essential cellular processes including transcription, mitochondrial biogenesis and replicative senescence. Previous reports suggest that REA is a multifunctional protein with important biological activity. …
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Deciphering the Molecular Basis of the Species Barrier in Prion Disease Using Bank Vole PrP
Prion disease is an infectious and fatal neurodegeneration condition which depends on the structural reconfiguration of a predominantly α-helical cellular protein called PrPC into a β-sheet rich conformer referred to as scrapie or PrPSc. The infectious nature of this conformer enables it to …
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NOVEL THERAPEUTIC APPROACHES EMERGING FROM HCN CHANNELS STRUCTURAL AND FUNCTIONAL STUDIES
… gated 1 (HCN1) channels are the molecular determinants of the cationic Ih current that regulates spontaneous electrical activity and synaptic integration in neurons. Mutations in the HCN1 gene have been linked to Early Infantile Epileptic Encephalopathy (EIEE) and a spectrum of neurodevelopmental …
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Eyelid conditioning in mice reveals an interaction between stress and familial Alzheimer's disease
Detailed behavioral analysis can provide valuable information on the underlying neural machinery supporting learning. An associative learning model called eyelid conditioning is often used to study mechanisms and modulatory processes governing cerebellar motor learning. Here, I implemented this …
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The Expression of the Zinc Finger Transcription Factor zDC Defines the Classical Dendritic Cell Lineage
… of the immune system due to their roles in the maintenance of immune tolerance and the induction of adaptive immune responses. However, distinguishing cDCs from other myeloid populations is complicated by the lack of highly specific cDC markers. For example, high expression of the …
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Impaired Ulk1 Ser555 Phosphorylation Promotes Amino Acid Reliance and Links Mitochondrial Inefficiency to Systemic Metabolic Inflexibility
… ability to switch between energetic substrates in response to nutrient availability—is essential for systemic energy balance and protection against metabolic disease. Loss of this adaptive capacity contributes to metabolic diseases marked by obesity, insulin resistance, and dyslipidemia, …
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Enforced Expression of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis
<p><strong>Enforced expression of <em>Tbx1</em> in fetal thymic epithelial cells antagonizes</strong></p> <p><strong>thymus organogenesis</strong></p> <p>Kim T. Cardenas</p> <p>The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At …
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Targeting the CD4 Binding Site of HIV
… obstacles to develop a broadly neutralizing antibody (bNAb) against HIV by vaccine mandate for methodical testing in order to understand and direct the immune response. A mouse model with the predicted human heavy chain variable domain of a bNAb precursor or mature version introduced into …
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Probing spatial and subunit-dependent signalling by the NMDA receptor
… neurotransmitter glutamate. NMDARs are essential in coupling electrical activity to biochemical signalling as a consequence of their high Ca2+ permeability. This Ca2+ influx acts as a secondary messenger to mediate neurodevelopment, synaptic plasticity, neuroprotection and neurodegeneration. The …
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The Function of LAT in T Cell Activation and Autoimmunity
<p>LAT (linker for activation of T cells) is an important transmembrane adaptor protein in TCR-mediated signaling. Upon TCR engagement, LAT associates with multiple proteins which allows for the activation of downstream signaling pathways. The interaction between LAT with phospholipase C …
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Functional relationships among lck kinase and the lat and grb2 adaptors in the intracellular signaling cascade of the tcr/cd3 complex: implications in thymic development and lymphocyte activation
… based on the nature of the recognized agent. In addition, they are responsible for the maintenance of cellular tolerance and homeostasis. T lymphocytes need to undergo processes of development, differentiation and activation in order to perform their functions, and for this purpose, they …
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The Emergence of Network Hyperexcitability and Functional Impairment in a Mouse Model of Alzheimer’s Disease
… feature of Alzheimer’s disease (AD), developing many years before symptomatic onset. Preceding the formation of amyloid plaques, extracellular Aβ has been shown to induce synaptic dysfunction and hyperexcitability in the hippocampus. This thesis aimed to elucidate the emergence of hippocampal …
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The Binding Properties and Functional Consequences of Ryr2-Cam Interaction
… of two parts. The first part focused on RyR2-CaM interaction. The second focused on synthetic RyR2 domain peptide (DPc10), which worked as a powerful molecular tool for RyR2 functional and structural studies.</p><p>CaM has been long identified as an important cardiac RyR regulator. Broad studies …
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Optogenetic dissection of the dopaminergic circuitry involved in memory consolidation
The ‘synaptic tagging-and-capture’ (STC) theory of cellular memory consolidation holds that memory persistence can be altered by prior or subsequent patterns of neural activity (Redondo & Morris 2011). The aim of this thesis was to develop a realistic model of everyday memory for mice and use the …
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Mechanistic Investigation of Genotype-Phenotype Correlations in PIK3R1-Related Diseases
The PIK3R1 gene encodes three proteins - p85$\alpha$, p50$\alpha$ and p55$\alpha$ - that are regulatory subunits of Class IA phosphoinositide 3-kinases (PI3Ks). These regulatory subunits heterodimerise with one of three catalytic subunit isoforms, namely p110$\alpha$, p110$\beta$, or p110$\delta$. …
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