Attempting to Induce Hypermobile Ehlers-Danlos Syndrome (hEDS) in C. Elegans
Abstract / Artist's Statement
The Ehlers-Danlos Syndromes (EDS) is a collection of 13 heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility1. Hypermobile Ehlers-Danlos (hEDS) is the most common subtype of EDS, accounting for approximately 80-90% of cases2 This obscurity can be attributed to hEDS being the only subtype of EDS without a known genetic cause, yet an autosomal dominant pattern of inheritance has been observed. Many studies have proposed TNXB as a candidate gene, as several heterozygous loss of function TNXB mutations have been shown to produce phenotypes diagnosable as hEDS1,5. TNXB encodes protein tenascin XB and has functions in collagen organization, metabolism, and binding in the extracellular matrix (ECM)7. In C. elegans, let-805 is an ortholog of TNXB8. Encoding for myotactin in the ECM, let-805 has roles in cell adhesion and muscle contraction. It is theorized that after the 2-fold stage of embryogenesis, myotactin maintains the spatial relationship between the muscle contraction apparatus and fibrous organelles, permitting proper mobility10. To replicate a heterozygous TNXB loss-of-function mutation as seen in hEDS, a partial knock down of let-805 in C. Elegans will be completed using reverse genetics RNAi technology. Worm knockdowns of let-805 are expected to produce phenotypes of death or increased mobility.
Attempting to Induce Hypermobile Ehlers-Danlos Syndrome (hEDS) in C. Elegans
UC South Ballroom
The Ehlers-Danlos Syndromes (EDS) is a collection of 13 heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility1. Hypermobile Ehlers-Danlos (hEDS) is the most common subtype of EDS, accounting for approximately 80-90% of cases2 This obscurity can be attributed to hEDS being the only subtype of EDS without a known genetic cause, yet an autosomal dominant pattern of inheritance has been observed. Many studies have proposed TNXB as a candidate gene, as several heterozygous loss of function TNXB mutations have been shown to produce phenotypes diagnosable as hEDS1,5. TNXB encodes protein tenascin XB and has functions in collagen organization, metabolism, and binding in the extracellular matrix (ECM)7. In C. elegans, let-805 is an ortholog of TNXB8. Encoding for myotactin in the ECM, let-805 has roles in cell adhesion and muscle contraction. It is theorized that after the 2-fold stage of embryogenesis, myotactin maintains the spatial relationship between the muscle contraction apparatus and fibrous organelles, permitting proper mobility10. To replicate a heterozygous TNXB loss-of-function mutation as seen in hEDS, a partial knock down of let-805 in C. Elegans will be completed using reverse genetics RNAi technology. Worm knockdowns of let-805 are expected to produce phenotypes of death or increased mobility.