Diaphragm Fiber Morphology of Ts65Dn Mice: A Model of Down Syndrome

Abstract

Down Syndrome (DS) is a developmental disability that results from triplication of chromosome 21. Roughly 40% of people with DS experience sleep apnea. Consistent with this finding, the Ts65Dn mouse model of DS was previously shown to display hypoxemia. Our interests center on the involvement of the nervous system and diaphragm in the etiology of hypoxemia in the Ts65Dn mouse. We hypothesized that Ts65Dn mice would exhibit a greater number of apneas and proportion of diaphragm fast twitch fibers, which may be associated with hypoxia in these mice. Male Ts65Dn mice and colony controls (WT) (n=8/group) were studied at 3 months of age using barometric plethysmography to determine the occurrence of apneas (mean±SD) over a thirty‐minute evaluation. At ten months of age the spinal cord and diaphragm tissues were harvested from mice under isoflurane anesthesia. Ts65Dn mice displayed more apneas (36.3±28.0) than WT (7.1±9.1) mice at 3 months of age (p<0.05). Diaphragm fiber type distributions and areas were determined from a subset of mice (n=2/group). Compared to WT controls, diaphragm muscles from Ts65Dn mice displayed smaller Type I/IIa and Type IIx fibers (18.8% and 5.6% smaller, respectively) and larger Type IIb fibers (17.7% larger). The distribution of Type I/IIa fibers was similar in Ts65Dn mice compared to WT (64.1% vs. 58.8%) and distribution of Type IIb fibers was less than WT (4.7% vs. 8.2%). The distribution of Type IIx fibers was similar between the groups (31.1% DS; 33.0% WT). Statistical analyses were not performed on diaphragm morphological comparisons due to the small sample size. Our preliminary analyses indicate the Type IIb fibers, in particular, of Ts65Dn diaphragms mice may be larger and less prevalent compared with control diaphragms. Our work continues to expand upon these findings by including a larger sample size to achieve appropriate statistical power and incorporating phrenic motoneuron counts in spinal cord sections.Support or Funding InformationSupported by NIH 1R15HD076379‐01A1, 1R15HD076379‐01A1S1, and 1R15HD076379‐01A1S2This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.