مورد إلكتروني
GNAS transcripts in skeletal progenitors:evidence for random asymmetric allelic expression of Gs alpha
| العنوان: | GNAS transcripts in skeletal progenitors:evidence for random asymmetric allelic expression of Gs alpha |
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| المصدر: | Michienzi , S , Cherman , N , Holmbeck , K , Funari , A , Collins , M T , Bianco , P , Robey , P G & Riminucci , M 2007 , ' GNAS transcripts in skeletal progenitors : evidence for random asymmetric allelic expression of Gs alpha ' , Human Molecular Genetics , vol. 16 , no. 16 , pp. 1921-30 . |
| بيانات النشر: | 2007-08-15 |
| تفاصيل مُضافة: | Michienzi, Stefano Cherman, Natasha Holmbeck, Kenn Funari, Alessia Collins, Michael T Bianco, Paolo Robey, Pamela Gehron Riminucci, Mara |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Activating mutations of the Gsalpha gene, encoded by the guanine nucleotide-binding protein, alpha stimulating (GNAS) locus located on chromosome 20q13, underlie different clinical phenotypes characterized by skeletal lesions [fibrous dysplasia (FD) of bone], extraskeletal diseases (mainly endocrine hyperfunction and skin hyperpigmentation) and variable combinations thereof [the McCune-Albright syndrome (MAS)]. This clinical heterogeneity is commonly assumed to reflect the post-zygotic origin of the mutation. However, the pattern of imprinting of the Gsalpha gene in some human post-natal tissues suggests that parental-dependent epigenetic mechanisms may also play a role in the phenotypic effect of the mutated GNAS genotype. FD lesions are generated by mutated clonogenic osteoprogenitors that reside, along with their normal counterparts, in FD bone marrow stroma. We analyzed the allelic expression pattern of Gsalpha and other GNAS alternative transcripts in the progeny of normal and mutated clonogenic stromal cells isolated in vitro from a series of informative FD/MAS patients. We report here for the first time that the two Gsalpha alleles are unequally expressed in both normal and FD-mutated stromal clones. However, in contrast to imprinting, the ratio of Gsalpha allelic expression is randomly established in different clones from the same patient. This result suggests that a parental-independent modulation of Gsalpha expression occurs in clonogenic osteoprogenitor cells and, at the single cell level, may impact on the severity of an FD lesion. Furthermore, we show that normal and mutated clonogenic stromal cells express GNAS alternative transcripts other than the common Gsalpha, some of which may be relevant to the development of FD. |
| مصطلحات الفهرس: | Adolescent, Adult, Alleles, Base Sequence, Bone Marrow/metabolism, Child, Chromogranins, Female, Fibrous Dysplasia of Bone/genetics, GTP-Binding Protein alpha Subunits, Gs/genetics, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Myoblasts, Skeletal/cytology, Reverse Transcriptase Polymerase Chain Reaction, Stromal Cells/cytology, article |
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| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | English |
| أرقام أخرى: | DAV oai:pure.atira.dk:publications/88951798-5d1c-4f08-95be-1b8bb07e6891 1322714392 |
| المصدر المساهم: | UNIV OF COPENHAGEN From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1322714392 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |