Deletion of the T-box transcription factor gene, Tbx1, in mice induces differential expression of genes associated with cleft palate in humans

Publication date: Available online 9 August 2018

Source: Archives of Oral Biology

Author(s): Noriko Funato, Hiromi Yanagisawa

ABSTRACT

Objective

We examined the function of the T-box transcription factor 1 (TBX1) in palatogenesis.

Design

Tbx1-knockout mice were examined by hematoxylin and eosin staining. Next, secondary palatal shelves dissected from wild type or Tbx1-knockout mice embryos at embryonic day 13.5 were investigated with microarray analysis, gene ontology analysis, and real-time quantitative polymerase chain reaction. We performed gene profiling of developing palatal shelves from wild type and Tbx1-knockout embryos. We also analyzed the association of mouse genes linked to cleft palate with biological processes and compared the results with those of our ontology analysis of dysregulated genes in Tbx1-knockout palatal shelves.

Results

Histological analysis of Tbx1-knockout palate with complete cleft palate at postnatal day 1 showed aplasia of secondary palates associated with a small mandible and a small tongue compared to wild type littermates. Gene ontology analysis indicated that genes associated with development of the nervous system, muscle, and biomineral tissue were dysregulated in Tbx1-knockout palatal shelves. Furthermore, in Tbx1-knockout palatal shelves, genes associated with human cleft palate, specifically, myosin heavy chain 3 (Myh3) and nebulin (Neb), were downregulated and gamma-aminobutyric acid type A receptor beta 1 subunit (Gabrb3) was upregulated.

Conclusions

Our findings demonstrate that TBX1 maintains normal growth and development of palatal shelves, mediated through the regulation of genes involved in muscle cell differentiation, nervous system development, and biomineral tissue development. Multiple factors in Tbx1-knockout mice may lead to various subtypes of cleft palate.

Graphical abstract

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Abdominal compartment syndrome secondary to megarectum and megasigmoid

A 31-year-old male patient with chronic constipation of unknown aetiology presented emergently with worsening nausea, vomiting and abdominal distension of one week duration. On examination, his abdomen was distended with minimal tenderness. A plain film of the abdomen demonstrated severe faecal loading. The patient was haemodynamically unstable on admission and appeared sick. An urgent CT abdomen and pelvis was conducted showing extensive rectal dilatation and associated proximal colonic stercoral perforation. The patient proceeded straight to theatre for laparotomy as his general condition was deteriorating rapidly. On transfer to the operating table, the patient suffered cardiopulmonary arrest. Resuscitation was immediately commenced. Abdominal compartment syndrome was suspected. Cardiac output was re-established following a midline laparotomy which acted relieve the abdominal pressure. The rectosigmoid faecal content was decompressed via an enterotomy. The perforated segment of transverse colon was resected and an end colostomy fashioned. A year later, the continuity of the bowel was re-established.

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Spontaneous bone regeneration in a large haemophilic pseudotumour of mandible

Pseudotumours of haemophilia (PTH) are locally expansile destructive haematomas which result in varying morbidity among haemophilic patients. Adequate haematological treatment and prophylaxis helps in preventing these haematomas. Currently, there is no uniform standard management protocol for this entity due to rarity of these lesions. PTH are seen in 1%–2% of the severe haemophilic patients. They may also be seen in moderate cases when adequate factor coverage is not provided or in cases with factor VIII inhibitors. We report a rare case of mandibular pseudotumour in a patient with moderate haemophilia and Glanzmann's thrombasthenia, treated successfully with decompression of the haematoma. Postdecompression, sequential radiography revealed spontaneous bone regeneration at the site of the lesion. With 2 years follow-up, the mandible had no residual lesion. This reveals the role and potential of conservative decompression even in cases with severe osteodestruction secondary to developing haematoma of the mandible in haemophilic patients.

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Delayed Presentation of Isolated Adrenocorticotropin Insufficiency after Nivolumab Therapy for Advanced Non-small-cell lung carcinoma (NSCLC)

We describe a 73-year-old man who developed adrenal insufficiency 7 months after completing nivolumab therapy for advanced non-small cell lung cancer. He presented with non-specific symptoms of malaise and fatigue with an insidious 13.6 kilogram weight loss, prompting an evaluation for disease progression, which was negative. Subsequent evaluation revealed isolated adrenocorticotropin insufficiency as the aetiology, attributed to a delayed side effect of nivolumab therapy.

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Beer anaphylaxis due to coriander as hidden allergen

Beer is one of the most widely consumed alcoholic beverage all over the world. Although the production and consumption of this beverage is diffuse, allergic reactions are very uncommonly reported, mainly due to wheat, yeast or hops allergy. More recently, many foods and drinks have been flavoured with spices, with a reported increase in allergic reactions. We report on a case of a young woman who experienced anaphylaxis due to coriander-flavoured beer. This is the first case of beer anaphylaxis due to coriander, which had been added to the beer as aromatising substance. As the presence of flavours is not always reported, they may be considered hidden allergens, whenever they are the cause of anaphylaxis to foods or beverages, the patient usually tolerated. In conclusion, allergic reactions to spices have to be considered in the patients with 'idiopathic' anaphylaxis induced by common foods, where spices had been hidden.

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Retroperitoneal schwannoma misdiagnosed as an ovarian malignancy

A 55-year-old woman presented to the hospital with abdominal discomfort over 3 months. Contrast-enhanced abdominal CT showed a 10x9x6.5 cm sized well-defined solid-cystic enhancing mass in the right pelvic cavity. Under general anaesthesia, exploratory laparotomy was performed on suspicion of ovarian malignancy. Pathological examination revealed a retroperitoneal schwannoma with highly ordered cellular component (Antoni A) and hypocellularity with predominantly loose myxoid component (Antoni B). On immunohistochemical staining, the sample showed typically positive result for S-100 in the cytoplasm of the tumour cells. Schwannomas are consisting only of Schwann cells and are most often non-malignant tumors. It is relatively slow growing and usually located in the head, neck and the extremities. Schwannomas are quite rare in the retroperitoneal region. The diagnosis of retroperitoneal schwannomas is often delayed and misdiagnosed as an adnexal tumour, especially locating in the pelvic cavity. Surgical complete resection of tumour is the treatment of choice and recurrence is unusual after complete resection.

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Trauma-induced dual vascular lesions in the liver-hepatic pseudoaneurysm with arteriohepatic venous fistula

Description 

A 17-year-old boy presented to the emergency triage with severe abdominal pain following blunt abdominal trauma. The patient was conscious, hypotensive with blood pressure 60/30 mm Hg, pulse rate 110/min and per abdomen examination revealed abdominal distension, tenderness, rigidity and free fluid. FAST (Focused Assessment with Sonography in Trauma) imaging revealed liver lacerations and haemoperitoneum. The patient was initially stabilised with inotropes, intravenous fluids and adequate analgesics and had to be directly taken up for emergency laparotomy as the ideal protocol of performing an emergency CT was forgone due to technical issues with the CT machine. Laparotomy revealed grade V liver injury with active bleeding and haemoperitoneum of about 2 L. Haemostatic agent (AbGel) and multiple intra-abdominal packs were used to stop bleeding, and massive blood transfusion protocol was activated. The patient was transferred to intensive care unit where he improved with conservative treatment. Before removing the intra-abdominal packs by relaparotomy,...

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