Biology & Sustainability
Three-Dimensional Analyses of Craniofacial and Oronasal Phenotypes in Ts65Dn Down Syndrome Mice Treated with EGCG, a Dyrk1a Inhibitor.
Document Type
Poster Presentation
Location
Indianapolis, IN
Subject Area
Biology & Sustainability
Start Date
11-4-2014 8:30 AM
End Date
11-4-2014 9:30 AM
Sponsor
Randall Roper (Indiana University/Purdue University at Indianapolis), John Starbuck (Indiana University/Purdue University at Indianapolis)
Description
Down syndrome (DS) originates from having three copies of chromosome 21 (i.e. Trisomy 21). DS is associated with many detrimental phenotypes including intellectual disabilities, heart defects, and abnormal craniofacial development. Additional complications common in individuals with DS arise from this altered craniofacial development such as obstructive sleep apnea which develops from restricted oronasal airways and an underdeveloped mandible. Ts65Dn mice are trisomic for about half of the orthologs on human chromosome 21 and display many phenotypes associated with DS including craniofacial abnormalities. Dyrk1a is found in three copies in Ts65Dn mice and individuals with DS and thought to be a root cause of the craniofacial phenotypes.
Epigallocatechin gallate (EGCG) is a green tea polyphenol and inhibitor of Dyrk1a activity. We hypothesize that decreased Dyrk1a activity in Ts65Dn mice will ameliorate the craniofacial phenotypes. To test our hypothesis we compared Ts65Dn mice with two or three copies of Dyrk1a and also compared Ts65Dn mice with or without EGCG treatment. Six week old mice were sacrificed and their heads imaged using micro-computed tomography (µCT). Dolphin software was used to measure oronasal airway volumes and collect 54 anatomical landmarks from mouse skulls and mandibles. Univariate 2-sample t-tests were used to evaluate oronasal airway volume differences, and a multivariate geometric morphometric approach known as Euclidean Distance Matrix Analysis (EDMA) was carried out to assess global and local differences in craniofacial and mandibular morphology between trisomic and euploid mice. Our preliminary results indicate that EGCG treatment or reduced copy number of Dyrk1a affects craniofacial morphology in Ts65Dn mice.
Three-Dimensional Analyses of Craniofacial and Oronasal Phenotypes in Ts65Dn Down Syndrome Mice Treated with EGCG, a Dyrk1a Inhibitor.
Indianapolis, IN
Down syndrome (DS) originates from having three copies of chromosome 21 (i.e. Trisomy 21). DS is associated with many detrimental phenotypes including intellectual disabilities, heart defects, and abnormal craniofacial development. Additional complications common in individuals with DS arise from this altered craniofacial development such as obstructive sleep apnea which develops from restricted oronasal airways and an underdeveloped mandible. Ts65Dn mice are trisomic for about half of the orthologs on human chromosome 21 and display many phenotypes associated with DS including craniofacial abnormalities. Dyrk1a is found in three copies in Ts65Dn mice and individuals with DS and thought to be a root cause of the craniofacial phenotypes.
Epigallocatechin gallate (EGCG) is a green tea polyphenol and inhibitor of Dyrk1a activity. We hypothesize that decreased Dyrk1a activity in Ts65Dn mice will ameliorate the craniofacial phenotypes. To test our hypothesis we compared Ts65Dn mice with two or three copies of Dyrk1a and also compared Ts65Dn mice with or without EGCG treatment. Six week old mice were sacrificed and their heads imaged using micro-computed tomography (µCT). Dolphin software was used to measure oronasal airway volumes and collect 54 anatomical landmarks from mouse skulls and mandibles. Univariate 2-sample t-tests were used to evaluate oronasal airway volume differences, and a multivariate geometric morphometric approach known as Euclidean Distance Matrix Analysis (EDMA) was carried out to assess global and local differences in craniofacial and mandibular morphology between trisomic and euploid mice. Our preliminary results indicate that EGCG treatment or reduced copy number of Dyrk1a affects craniofacial morphology in Ts65Dn mice.