CTNNB1 mutations and estrogen receptor expression in neuromuscular choristoma and its associated fibromatosis

Neuromuscular choristoma (NMC) is a very rare, developmental malformation characterized by the endoneurial intercalation of mature muscle fibers among peripheral nerve fibers. NMC typically arises in the major proximal peripheral nerves, most commonly the sciatic nerve, and may involve the lumbosacral and brachial plexus. Patients present clinically with progressive neuropathy or plexopathy. NMC is strongly associated with development of a fibromatosis, histologically identical to conventional desmoid-type fibromatosis (NMC-fibromatosis). The development of NMC-fibromatosis is often precipitated by iatrogenic trauma (ie, biopsy). Desmoid-type fibromatosis is characterized by CTNNB1 exon 3 mutations, which result in aberrant nuclear \u3b2-catenin localization and dysregulated canonical Wnt signaling. In contrast, the pathogenesis of NMC and NMC-fibromatosis is unknown. Desmoid-type fibromatosis expresses estrogen receptors (ER), specifically the ER-beta isoform (ER\u3b2), and endocrine therapies may be used in surgically unresectable cases. In contrast, the ER expression profile of NMC-fibromatosis is unknown. We evaluated a series of NMC and NMC-fibromatosis for CTNNB1 mutations, \u3b2-catenin expression, and ER isoform expression. Five NMCs occurred in 2 female and 3 male patients (median age: 14 y, range <1 to 42 y), as masses involving the sciatic nerve (N=4) or brachial plexus (N=1). Four (of 5) NMCs had CTNNB1 mutations: 3 c.134 C>T (p.S45F) and 1 c.121 A>G (p.T41A). Four patients subsequently developed NMC-fibromatosis, and all 4 cases contained CTNNB1 mutations, including 1 p.T41A and 3 p.S45F mutations. In 3 patients, the NMC and NMC-fibromatosis had identical CTNNB1 mutations. Only 1 NMC had no detectable CTNNB1 mutation; however, the patient's subsequent NMCfibromatosis had a CTNNB1 p.T41A mutation. All NMC and NMC-fibromatosis showed aberrant nuclear localization of \u3b2-catenin, nuclear ER\u3b2 expression, and no ER\u3b1 expression. The presence of CTNNB1 mutations both in NMC and NMC-fibromatosis may be a shared molecular genetic abnormality underlying their pathogenesis

Characterization of TIEG1 KO muscle structure with diffusion weighted-MRI

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TGFb inducible early gene-1 knockout mice display defects in the molecular structure of tendon fibers.

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Molecular structure of tail tendon fibers in TIEG1 knockout mice using synchrotron diffraction technology

International audienceMolecular structure of tail tendon fibers in TIEG1 knockout mice using synchrotron diffraction technology. J Appl Physiol 108: 1706-1710, 2010. First published April 8, 2010; doi:10.1152/japplphysiol. 00356.2010.-The purpose of this study was to characterize the effect of TIEG1 on the molecular structure of collagen within tail tendon fibers using 3-moold female C57BL/6 wild-type (WT) and TIEG1 KO mice. Synchrotron X-ray microdiffraction experiments were carried out on single tendon fibers extracted from the WT and TIEG1 KO dorsal tail tendon. The fibers were scanned in the radial direction, and X-ray patterns were obtained. From these patterns, the meridional direction was analyzed through X-ray intensity profile. In addition, collagen content was investigated using hydroxyproline assays, and qualitative real-time PCR experiments were performed on RNA isolated from fibroblasts to examine specific gene expression changes. The results showed different X-ray diffraction patterns between WT and TIEG1 KO tendon fibers, indicating a disorganization of the collagen structure for the TIEG1 KO compared with WT mice. Furthermore, the analyses of the X-ray intensity profiles exhibited a higher (23 angstrom) period of collagen for the TIEG1 KO compared with the WT mice. The results of the hydroxyproline assays revealed a significant decrease in the TIEG1 KO compared with WT mice, leading to a decrease in the total amount of collagen present within the TIEG1 KO tendons. Moreover, qualitative real-time PCR results showed differences in the expression profiles of specific genes known to play important roles in tendon fiber development. These data further elucidate the role of TIEG1 on tendon structure and could explain the previous defects in the structure-function relationship found for TIEG1 KO tendon fibers

Loss of KLF10 expression does not affect the passive properties of single myofibrils

International audienceThe purpose of this study was to gain insight into the origin of the passive behavior observed in KLF10 KO soleus and EDL muscles, at the fiber scale and at the myofibril (titin) scale. The conclusion from the results of this study is that the observed fibre-type specific changes in passive force in KLF10 KO mice muscles are not caused by sarcomere intrinsic structures but must originate outside the sarcomeres, likely in the collagen-based extracellular matrix