Methionine sulfoxide reductase B3 (MsrB3) is a protein repair enzyme that specifically reduces methionine-R-sulfoxide to methionine. A recent genetic study showed that the MSRB3 gene is associated with autosomal recessive hearing loss in human deafness DFNB74. However, the precise role of MSRB3 in the auditory system and the pathogenesis of hearing loss have not yet been determined. This work is the first to generate MsrB3 knockout mice to elucidate the possible pathological mechanisms of hearing loss observed in DFNB74 patients. We found that homozygous MsrB3(-/-) mice were profoundly deaf and had largely unaffected vestibular function, whereas heterozygous MsrB3(+/-) mice exhibited normal hearing similar to that of wild-type mice. The MsrB3 protein is expressed in the sensory epithelia of the cochlear and vestibular tissues, beginning at E15.5 and E13.5, respectively. Interestingly, MsrB3 is densely localized at the base of stereocilia on the apical surface of auditory hair cells. MsrB3 deficiency led to progressive degeneration of stereociliary bundles starting at P8, followed by a loss of hair cells, resulting in profound deafness in MsrB3(-/-) mice. The hair cell loss appeared to be mediated by apoptotic cell death, which was measured using TUNEL and caspase 3 immunocytochemistry. Taken together, our data suggest that MsrB3 plays an essential role in maintaining the integrity of hair cells, possibly explaining the pathogenesis of DFNB74 deafness in humans caused by MSRB3 deficiency.
BackgroundDiabetes is characterized by hyperglycemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The aim of the present study was to investigate the effects of ginger on various tissues (i.e., pancreas, kidney, and liver) and insulin resistance in streptozotocin-induced diabetic mice. The pleasant aroma of ginger comes from the constituents present in its volatile oil, while its non-volatile pungent phytochemicals consist of gingerols, shogaols, and paradols.MethodsThis research was conducted to determine the effects of 6-shogaol administration on blood glucose and insulin production in type 1 diabetic mice. Mice were intraperitoneally injected with shogaol at 5 or 10 mg/kg body weight. Untreated mice were injected with an equivalent volume of buffer, three times a week for 2 weeks. The animals were randomly divided into four experimental groups: control group mice (n = 3) were given an intraperitoneal (IP) injection of streptozotocin (STZ) vehicle (1 mL citrate buffer/100 g body weight) at day 1 and received an IP injection of 6-shogaol vehicle [1 mL buffer (0.5% DMSO, 10% Tween 20, and 89.5% PBS)/100 g body weight] every other day for 4 consecutive days.Results6-Shogaol exhibited an antidiabetic effect by significantly decreased the level of blood glucose, body weight and attenuated the above pathological changes to the normal levels in the diabetic mice, and has effect against pancreas, kidney, liver damage in the diabetic mice. Since, 6-shogaol prevented the damage for STZ induced stress.Conclusion6-Shogaol can be used as a therapeutic agent for preventing complications in diabetic patients. Diabetic treatment consider the 6-shogaol as a pharmatheuticals or combination drug with herbal plant or others 6-shogaol may be a good therapeutic drug because it covers not only pancreatic β-cell but also liver and kidney. Ginger may be ideal because they contain a variety of pharmacological compounds with different known pharmacological actions.
Many genome-edited animals have been produced using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology to edit specific genes.However, there are few guidelines for the application of this technique to cattle. The goal of this study was to produce trait-improved cattle using the genome-editing technology CRISPR-Cas9. Myostatin (MSTN) was selected as a target locus, and synthetic mRNA of sgRNA and Cas9 were microinjected into fertilized bovine embryos in vitro. As a result, 17 healthy calves were born, and three of them showed MSTN mutation rates of 10.5%, 45.4%, and 99.9%, respectively. Importantly, the offspring with the 99.9% MSTN mutation rate had a biallelic mutation (-12 bps) and a doublemuscling phenotype. In conclusion, we demonstrate that the genome-editing technology CRISPR-Cas9 can produce genetically modified calves with improved traits.
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