Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome

Abstract

A high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice. Dp16 mice demonstrated craniofacial hypoplasia, especially in the ventral part of the skull and the mandible, and rostrally positioned hyoid. These changes were accompanied with a shorter length and smaller cross-sectional area of the upper airway, resulting in a significantly reduced upper airway volume in Dp16 mice. Our non-invasive approach, a combination of computational fluid dynamics and high-resolution micro-CT imaging, revealed a higher negative pressure inside the airway of Dp16 mice compared to wild-type littermates, showing the potential risk of upper airway collapse. Our study indicated that Dp16 mice can be a useful model to examine the pathophysiology of increased upper airway collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and sleep anomalies.

Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down syndrome-related phenotypes

“…In agreement with this, Dp1Tyb mice have shorter body and femur length ( Thomas et al, 2020 ), smaller crania and mandibles, mid-facial hypoplasia and cranial doming ( Toussaint et al, 2021 ). Similar craniofacial changes have been seen in the Dp1Yey mouse strain ( Starbuck et al, 2014 ; Takahashi et al, 2020 ), which, like Dp1Tyb mice, was generated by Cre/loxP chromosome engineering and has an extra copy of the same Hsa21-orthologous genes as Dp1Tyb ( Li et al, 2007 ). Indeed, where comparable analysis has been carried out, Dp1Tyb and Dp1Yey mice have very similar phenotypes ( ).…”

“…The motor deficits in these mice may be partly due to motor neuron loss, which we also found in human DS ( Watson-Scales et al, 2018 ). The disrupted sleep of Dp1Tyb mice may have a neurological basis, but analysis of Dp1Yey mice showed reduced upper-airway volume, suggesting that apnoea may affect sleep in these animals ( Takahashi et al, 2020 ).…”

Altered responses of end‐expiratory lung volume and upper airway patency to body posture in diet‐induced obese mice

“…Cross‐sectional areas (CSA) of the upper airway were measured with OsiriX 10.0 (Pixmeo) as detailed previously (Takahashi et al, 2020 ). CSA in the end‐expiration phase was measured at the following two locations: (1) at the end of the soft palate (caudal CSA; Brennick et al, 2009 ) and (2) 2 mm caudal to the edge of the hard palate (rostral CSA) at which the upper airway is closely surrounded by bones (Takahashi et al, 2020 ).…”

Anesthesia management in a Down syndrome patient with difficult intubation: Case report

“…Complementary drugs, such as acetaminophen and non-steroids, can help reduce the dose of narcotics. These patients should be monitored in recovery room and then transferred to ICU [7,9].…”