Phenotype-genotype relationships in Xenopus sox9 crispants provide insights into campomelic dysplasia and vertebrate jaw evolution.

Since CRISPR-based genome editing technology works effectively in the diploid frog Xenopus tropicalis, a growing number of studies have successfully modeled human genetic diseases in this species. However, most of their targets were limited to non-syndromic diseases that exhibit abnormalities in a small fraction of tissues or organs in the body. This is likely because of the complexity of interpreting the phenotypic variations resulting from somatic mosaic mutations generated in the founder animals (crispants). In this study, we attempted to model the syndromic disease campomelic dysplasia (CD) by generating sox9 crispants in X. tropicalis. The resulting crispants failed to form neural crest cells at neurula stages and exhibited various combinations of jaw, gill, ear, heart, and gut defects at tadpole stages, recapitulating part of the syndromic phenotype of CD patients. Genotyping of the crispants with a variety of allelic series of mutations suggested that the heart and gut defects depend primarily on frame-shift mutations expected to be null, whereas the jaw, gill, and ear defects could be induced not only by such mutations but also by in-frame deletion mutations expected to delete part of the jawed vertebrate-specific domain from the encoded Sox9 protein. These results demonstrate that Xenopus crispants are useful for investigating the phenotype-genotype relationships behind syndromic diseases and examining the tissue-specific role of each functional domain within a single protein, providing novel insights into vertebrate jaw evolution.

Age-related composition changes in swallowing-related muscles: a Dixon MRI study.

BACKGROUND: Dysphagia is considered a social problem in the super-aging society. However, age-related changes in swallowing-related muscles have not been fully deciphered. AIMS: We aimed to identify intramuscular fatty infiltration and muscle atrophy in multiple swallowing-related muscles on magnetic resonance imaging (MRI). Moreover, an appropriate muscle strength parameter for the evaluation of swallowing-related muscle mass was examined. METHODS: We analyzed the Dixon MRI results of 20 elderly and 20 young adults without head and neck cancer, stroke, neuromuscular disease, or whole-body sarcopenia to evaluate intramuscular fatty infiltration (IMF) and lean muscle mass (LMM) in the tongue, geniohyoid, and pharyngeal muscles. The pharyngeal lumen size was also assessed. Tongue pressure, jaw-opening strength, occlusal force, and head-lifting strength were evaluated within a week before and after MRI. RESULTS: Aging significantly affected the IMF of the swallowing-related muscles, and the tongue muscle was most affected, followed by the pharyngeal muscle and then the geniohyoid muscle. Only the LMM of the geniohyoid muscle significantly decreased with aging. The pharyngeal lumen size did not significantly differ between the elderly and young participants, and only tongue pressure was significantly correlated with tongue, geniohyoid, and pharyngeal muscle mass. CONCLUSIONS: IMF is primarily associated with age-related composition changes in swallowing-related muscles, and it is commonly observed in the tongue and pharyngeal muscles. The geniohyoid muscle is more at risk of muscle atrophy rather than fatty infiltration. In addition, tongue pressure can be a parameter for the evaluation of swallowing-related muscle mass.

Relationship between Rate of Force Development of Tongue Pressure and Physical Performance.

In the assessment of skeletal muscle strength, rate of force development (RFD) is clinically identified as a functional index that reflects the effects of aging, but there are few reports on RFD of the tongue. The purpose of this study was to examine the relationship between RFD of tongue pressure (RFD-TP) and oral and whole-body physical performance in older adults, and to clarify its characteristics. We enrolled adults aged ≥65 years with pathological occlusal contact in premolar and molar regions of teeth in the Tamba-Sasayama area, Japan, from 2017 to 2018. Maximum tongue pressure (MTP) and the speed to reach the maximum tongue pressure (RFD-TP) were evaluated as measures of tongue function. Oral functions related to objective measures of tongue function, such as repetitive saliva swallowing test, oral diadochokinesis, and physical status or performance, such as mini mental state examination, body mass index, skeletal mass index, knee extension force, one-leg standing time, grip strength, walking speed, timed up-and-go test, and five-time chair stand speed was evaluated. No significant correlation was found between MTP and age, but RFD-TP had a significant negative correlation with age. Neither RFD-TP nor MTP showed a significant correlation with oral function. RFD-TP was associated with physical performance, such as knee extension force and one-leg standing time. RFD-TP is more sensitive to aging than MTP. In addition, RFD-TP is related to physical performance and may be useful for the early detection of frailty.

[Case of Heerfordt's syndrome with prolonged peripheral nerve involvement].

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.