May 18, 2017 Defect of the medial cerebellum in Rac1\/Rac3-DKO mouse. Credit: Kobe University <\/p>\n
Opitz G\/BBB (Opitz) syndrome is a hereditary disorder that affects people in different ways, causing malformations in medial (midline) organs and structures, intellectual disability and developmental disorders. Scientists have revealed a new control mechanism for the gene that causes this disorder, a discovery that could help in developing treatment for the syndrome. The findings were published on May 16 in the online edition of Development. <\/p>\n
A group of scientists led by Associate Professor UEYAMA Takehiko and Professor SAITO Naoaki (both from the Kobe University Biosignal Research Center) and members of Kyoto Prefectural University of Medicine carried out this research. <\/p>\n
Professor Ueyama expressed his hopes that this discovery would contribute to \"revealing the underlying mechanism that explains the range of symptoms caused by Opitz syndrome, a disease that has different effects on individual patients, even within the same family\". <\/p>\n
Opitz syndrome occurs for at least 1 in every 10,000-50,000 people. It is a hereditary disorder that causes a wide range of physical malformations in midline structures of organs, including in the brain, the face, the heart, the larynx and pharynx, the trachea and esophagus, urinary organs and genitals. <\/p>\n
Previous findings identified Midline 1 (MID1) as the gene responsible for Opitz syndrome. The functional decline of MID1 causes the congenital disorders described above, but it is still unclear why these symptoms are so varied among individual patients. Treatment methods are yet to be fixed, and surgical therapy is currently the main treatment. <\/p>\n
The research team focused on cerebellar granule neurons, a type of neurons with the largest population in the brain, and a signaling protein\/molecule called Rac which functions in cerebellar granule neurons during cerebellar development. The team created a \"knockout\" mouse with the Rac protein deleted. They discovered that this mouse experienced severe walking impairment because of the loss of the internal granule layer in the medial cerebellum. Next, they extracted the cerebellar granule neurons affected by the deleted Rac from the medial cerebellum. Using DNA microarrays they examined these neurons and discovered reduced expression of MID1, the causative gene of Opitz syndrome. This showed that Rac had been regulating the expression of Mid1, and when Rac was deleted, MID1 stopped functioning correctly in the mouse. <\/p>\n
They also discovered a cell signaling pathway in which Rac-Mid1-mTOR form a complex and contribute to the differentiation and maturation of cerebellar granule cells. <\/p>\n
The individual variability in these cell signaling pathways could be a cause of the broad range in the symptoms caused by Opitz syndrome. These findings could lead to development of a new treatment for Opitz syndrome that targets cell signaling. <\/p>\n
Explore further: Scientist models Smith-Lemli-Opitz syndrome in adult stem cells <\/p>\n
More information: Takashi Nakamura et al. Novel role of Rac-Mid1 signaling in medial cerebellar development, Development (2017). DOI: 10.1242\/dev.147900<\/p>\n
Journal reference: Development <\/p>\n
Provided by: Kobe University <\/p>\n
In the earliest stages of embryonic development, a protein known as TET1 may be the factor that tips the balance toward health or disease. The first evidence for this vital role of TET1 is presented in Nature Genetics by ... <\/p>\n
Stop-and-go traffic is typically a source of frustration, an unneccesary hold-up on the path from point A to point B. But when it comes to the molecular machinery that copies our DNA into RNA, a stop right at the beginning ... <\/p>\n
A new study of inherited genetic risk indicates that common genetic variations throughout the genome act in addition to rare, deleterious mutations in autism-associated genes to create risk for autism. <\/p>\n
Sharing medical information, including genomic data, has the potential to benefit public health. However, companies that generate that information have a legal right to protect it as a trade secret. Legal and ethical conflict ... <\/p>\n
A landmark study led by UNC School of Medicine researchers has identified the first genetic locus for anorexia nervosa and has revealed that there may also be metabolic underpinnings to this potentially deadly illness. <\/p>\n
When a group of researchers in the Undiagnosed Disease Network at Baylor College of Medicine realized they were spending days combing through databases searching for information regarding gene variants, they decided to do ... <\/p>\n
Please sign in to add a comment. Registration is free, and takes less than a minute. Read more <\/p>\n
<\/p>\n
See more here: May 18, 2017 Defect of the medial cerebellum in Rac1\/Rac3-DKO mouse. Credit: Kobe University Opitz G\/BBB (Opitz) syndrome is a hereditary disorder that affects people in different ways, causing malformations in medial (midline) organs and structures, intellectual disability and developmental disorders Continue reading
\nControl mechanism unveiled for gene that causes Opitz syndrome - Medical Xpress<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"