scholarly journals Finding the Unicorn, a New Mouse Model of Midfacial Clefting

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Brandi Lantz ◽  
Casey White ◽  
Xinyun Liu ◽  
Yong Wan ◽  
George Gabriel ◽  
...  

Human midfacial clefting is a rare subset of orofacial clefting and in severe cases, the cleft separates the nostrils splitting the nose into two independent structures. To begin to understand the morphological and genetic causes of midfacial clefting we recovered the Unicorn mouse line. Unicorn embryos develop a complete midfacial cleft through the lip, and snout closely modelling human midfacial clefting. The Unicorn mouse line has ethylnitrosourea (ENU)-induced missense mutations in Raldh2 and Leo1. The mutations segregate with the cleft face phenotype. Importantly, the nasal cartilages and surrounding bones are patterned and develop normal morphology, except for the lateral displacement because of the cleft. We conclude that the midfacial cleft arises from the failure of the medial convergence of the paired medial nasal prominences between E10.5 to E11.5 rather than defective cell proliferation and death. Our work uncovers a novel mouse model and mechanism for the etiology of midfacial clefting.

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 110-OR
Author(s):  
SHINSUKE TOKUMOTO ◽  
DAISUKE YABE ◽  
HISATO TATSUOKA ◽  
RYOTA USUI ◽  
MUHAMMAD FAUZI ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1120
Author(s):  
Dae Woon Choi ◽  
Sun Young Jung ◽  
Gun-Dong Kim ◽  
So-Young Lee ◽  
Hee Soon Shin

Allergic diseases, including atopic dermatitis (AD), induce type 2 helper T (Th2) cell-dominant immune responses. Miquelianin (quercetin 3-O-glucuronide, MQL) is an active compound in Rosae multiflorae fructus extract with anti-allergic properties. Here, we investigate the anti-allergic effects of MQL in an ovalbumin (OVA)-induced Th2-dominant mouse model and the associated mechanisms. Oral MQL suppressed cytokine and IL-2 production and proliferation of Th2 cells and upregulated heme oxygenase-1 (HO-1) in splenocytes. Ex vivo MQL suppressed Th1- and Th2-related immune responses by inhibiting CD4+ T cell proliferation, and upregulated HO-1 in CD4+ T cells by activating C-Raf–ERK1/2–Nrf2 pathway via induction of reactive oxygen species generation. In a trimellitic anhydride-induced AD-like mouse model, both topical and oral MQL ameliorated AD symptoms by suppressing Th2 immune responses. Our results suggest that MQL is a potential therapeutic agent for CD4+ T cell-mediated diseases, including allergic diseases.


2010 ◽  
Vol 40 (4) ◽  
pp. 998-1010 ◽  
Author(s):  
William F. Carson ◽  
Karen A. Cavassani ◽  
Toshihiro Ito ◽  
Matthew Schaller ◽  
Makoto Ishii ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Shaoteng Wang ◽  
Micaela Tatman ◽  
Mervyn J. Monteiro

Abstract Missense mutations in UBQLN2 cause X-linked dominant inheritance of amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). UBQLN2 belongs to a family of four highly homologous proteins expressed in humans that play diverse roles in maintaining proteostasis, but whether one isoform can substitute for another is not known. Here, we tested whether overexpression of UBQLN1 can alleviate disease in the P497S UBQLN2 mouse model of ALS/FTD by crossing transgenic (Tg) mouse lines expressing the two proteins and characterizing the resulting genotypes using a battery of pathologic and behavioral tests. The pathologic findings revealed UBQLN1 overexpression dramatically reduced the burden of UBQLN2 inclusions, neuronal loss and disturbances in proteostasis in double Tg mice compared to single P497S Tg mice. The beneficial effects of UBQLN1 overexpression were primarily confirmed by behavioral improvements seen in rotarod performance and grip strength in male, but not female mice. Paradoxically, although UBQLN1 overexpression reduced pathologic signatures of disease in P497S Tg mice, female mice had larger percentage of body weight loss than males, and this correlated with a corresponding lack of behavioral improvements in the females. These findings lead us to speculate that methods to upregulate UBQLN1 expression may reduce pathogenicity caused by UBQLN2 mutations, but may also lead to gender-specific outcomes that will have to be carefully weighed with the therapeutic benefits of UBQLN1 upregulation.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Minjung Song ◽  
Dong Ki Park ◽  
Hye-Jin Park

Antrodia camphoratagrown on germinated brown rice (CBR) was prepared to suppress melanoma development. CBR extracts were divided into hexane, EtOAc, BuOH, and water fractions. Among all the fractions, EtOAc fraction showed the best suppressive effect on B16F10 melanoma cell proliferation by CCK-8 assay. It also showed the increased cell death and the changed cellular morphology after CBR treatment. Annexin V-FITC/PI, flow cytometry, and western blotting were performed to elucidate anticancer activity of CBR. The results showed that CBR induced p53-mediated apoptotic cell death of B16F10. CBR EtOAc treatment increased melanin content and melanogenesis-related proteins of MITF and TRP-1 expressions, which supports its anticancer activity. Its potential as an anticancer agent was further investigated in tumor-xenografted mouse model. In melanoma-xenografted mouse model, melanoma tumor growth was significantly suppressed under CBR EtOAc fraction treatment. HPLC analysis of CBR extract showed peak of adenosine. In conclusion, CBR extracts notably inhibited B16F10 melanoma cell proliferation through the p53-mediated apoptosis induction and increased melanogenesis. These findings suggest that CBR EtOAc fraction can act as an effective anticancer agent to treat melanoma.


2018 ◽  
Vol 29 (12) ◽  
pp. 1756-1763
Author(s):  
Eun Jung Jun ◽  
Ho-Young Song ◽  
Jung-Hoon Park ◽  
Yoon Sung Bae ◽  
Bjorn Paulson ◽  
...  

EBioMedicine ◽  
2017 ◽  
Vol 15 ◽  
pp. 163-172 ◽  
Author(s):  
Sohei Tsukita ◽  
Tetsuya Yamada ◽  
Kei Takahashi ◽  
Yuichiro Munakata ◽  
Shinichiro Hosaka ◽  
...  

2017 ◽  
Vol 1 (7) ◽  
pp. 965-979 ◽  
Author(s):  
Tingting Wu ◽  
Jinyong Xu ◽  
Shengchun Xu ◽  
Lianzhong Wu ◽  
Youyu Zhu ◽  
...  

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