We further show that SYK centrally mediates signaling upstream of caspase-1 and caspase-8 activation and principally up-regulates NF-κB and IL-1β signaling in <i>Pstpip2<sup>cmo</sup></i> mice and thereby induces <i>cmo.</i> These results provide a rationale for directly targeting SYK and its downstream signaling components in CRMO.
In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures.
This study provides evidence that the OCT-derived VIT/RPE-relative intensity may be useful as a quantitative and objective marker of disease activity and treatment response in uveitis complicated by CMO.
Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials.We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively.
Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials.We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively.
Exome sequencing reveals RAG1 mutations in a child with autoimmunity and sterile chronic multifocal osteomyelitis evolving into disseminated granulomatous disease.
Here, we demonstrate that attenuated extracellular-signal regulated kinase (ERK)1 and 2 signaling in response to TLR4 activation results in failure to induce IL-10 expression in monocytes from CRMO patients.
The genes responsible for Majeed syndrome (LPIN2), murine chronic multifocal osteomyelitis (pstpip2), and cherubism (SH3BP2 and possibly PTPN11) have been identified.
The genes responsible for Majeed syndrome (LPIN2), murine chronic multifocal osteomyelitis (pstpip2), and cherubism (SH3BP2 and possibly PTPN11) have been identified.
Mutation screening in RANK and the genes PIGN and KIAA1468 led to detection of two variants (one in RANK and one in PIGN), which are in linkage disequilibrium with the rare D18S60 allele, but not independently associated with CRMO.
Mutation screening in RANK and the genes PIGN and KIAA1468 led to detection of two variants (one in RANK and one in PIGN), which are in linkage disequilibrium with the rare D18S60 allele, but not independently associated with CRMO.
Mutation screening in RANK and the genes PIGN and KIAA1468 led to detection of two variants (one in RANK and one in PIGN), which are in linkage disequilibrium with the rare D18S60 allele, but not independently associated with CRMO.
We further show that SYK centrally mediates signaling upstream of caspase-1 and caspase-8 activation and principally up-regulates NF-κB and IL-1β signaling in <i>Pstpip2<sup>cmo</sup></i> mice and thereby induces <i>cmo.</i> These results provide a rationale for directly targeting SYK and its downstream signaling components in CRMO.