The effect of Col5a1 knockout in Prx1+ progenitors on tendon and vascular connective tissue morphology in the developing limb

Colling, Haley

Undergraduate Honors Thesis

The effect of Col5a1 knockout in Prx1+ progenitors on tendon and vascular connective tissue morphology in the developing limb Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/9c67wp190

Abstract

Healthy structure and function of connective tissues is driven by proper extracellular matrix (ECM) composition and architecture. In connective tissues of the musculoskeletal system, such as tendons or the tunica adventitia surrounding blood vessels, type I collagen fibrils are abundant and the primary contributor to establishing proper tissue architecture and function. Initiation of type I collagen fibrillogenesis requires type V collagen. In humans, genetic defects in COL5A1 are associated with a heritable connective tissue disorder, Ehlers-Danlos syndrome, which also presents as defects in blood vessels. While these phenotypes have been studied in murine post-natal tissues, the development of these tissue abnormalities remains poorly understood. To address this gap, we generated a transgenic mouse model that knocks out Col5a1 synthesis in connective tissue cells (Prx1+) and assessed embryonic limbs for morphological changes in connective tissues using immunofluorescence. Wrist contracture and altered connective tissues (tendon) were observed in Prx1^Cre/+;Col5a1^fl/fl forelimbs. While we observed ecchymosis near the scapula in the mutants, there was minimal evidence of morphological changes in the vasculature of the limbs. However, we observed that lack of COL5A1 in Prx1^Cre/+ connective tissue cells lead to altered tendon morphology in homozygotes during embryogenesis, indicating that COL5A1 is necessary for normal tendon development prior to maturation of musculoskeletal connective tissues.

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