Functional and genetic studies in the macular degeneration genes ELOVL4 and HTRA1.

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Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Cameron, D. Joshua.
Title Functional and genetic studies in the macular degeneration genes ELOVL4 and HTRA1.
Date 2007-08
Description Macular degeneration is a debilitating eye disease and is the leading cause of blindness in the developed world affecting both young and old alike. The primary hallmarks of macular degeneration are photoreceptor degeneration and retinal pigment epithelium atrophy in the central retina. An autosomal dominant form of juvenile macular degeneration, Stargardt-like macular dystrophy 3 (STGD3), is caused by mutation in the elongation of very long chain fatty acids protein 4 (ELOVL4). However, little is known about ELOVL4's function or how mutations results in macular degeneration. Genetically manipulated mice expressing a human mutant ELOVL4 protein, containing a premature stop codon in Elov14, or lacking a functional copy of Elov14 are used to investigate both the cause of STGD3 and the function of ELOVL4. Only mice expressing a mutant ELOVL4 protein develop a STGD3-like phenotype, suggestive of a dominant negative cause of STGD3. Elov14 haploinsufficient mice do not develop a STG3-like phenotype further implicating a dominant negative mechanism. Mice without a functional copy of ELov14 die within a few hours after birth, have an impaired skin permeability barrier and fall to produce sufficient C28 and longer chain fatty acids, suggesting an essential role of Elov14 in very long chain fatty acid (>2) elongation. Age-related macular degeneration (AMD) is a complex disease with a poorly understood etiology. Two forms of advanced AMD, geographic atrophy and choroidal neovascularization, represent degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in the macula without visual loss are a precursor of advanced AMD. Based on previous studies in choroidal neovascularization, an expanded Utah cohort is used to analyze the association of a single nucleotide polymosphism in the promoter of HTRA1 with geographic atrophy, and soft confluent drusen. Geographic atrophyp is significantly associated with the A allele in the HTRA1 single nucleotide polymorphism rs11200638. These results increase our understanding of the etiology of AMD and provide a novel gene to investigate for future studies.
Type Text
Publisher University of Utah
Subject Mice; Electrophysiology
Subject MESH Retinal Degeneration; Genetics
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Functional and genetic studies in the macular degeneration genes ELOVL4 and HTRA1." Spencer S. Eccles Health Sciences Library. Print version of "Functional and genetic studies in the macular degeneration genes ELOVL4 and HTRA1." available at J. Willard Marriott Library Special Collection. RE16.5 2007 .C34.
Rights Management © D. Joshua Cameron.
Format Medium application/pdf
Identifier us-etd2,127
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Interdepartmental Program in Neuroscience.
ARK ark:/87278/s6794k9c
Setname ir_etd
Date Created 2012-04-23
Date Modified 2012-04-23
ID 193691
Reference URL