Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients. Existing NF1 mutant mice mimic individual aspects of NF1, but none comprehensively models the disease. We describe a potentially novel Yucatan miniswine model bearing a heterozygotic mutation in NF1 (exon 42 deletion) orthologous to a mutation found in NF1 patients. NF1+/ex42del miniswine phenocopy the wide range of manifestations seen in NF1 patients, including café au lait spots, neurofibromas, axillary freckling, and neurological defects in learning and memory. Molecular analyses verified reduced neurofibromin expression in swine NF1+/ex42del fibroblasts, as well as hyperactivation of Ras, as measured by increased expression of its downstream effectors, phosphorylated ERK1/2, SIAH, and the checkpoint regulators p53 and p21. Consistent with altered pain signaling in NF1, dysregulation of calcium and sodium channels wa...Continue Reading
Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis
Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients
Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues
Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain
Superficial neurofibroma: a lesion with unique MRI characteristics in patients with neurofibromatosis type 1
Stimulus-evoked release of neuropeptides is enhanced in sensory neurons from mice with a heterozygous mutation of the Nf1 gene
Inhibition of RAS-mediated transformation and tumorigenesis by targeting the downstream E3 ubiquitin ligase seven in absentia homologue
Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer
Comparison of histochemical methods for murine eosinophil detection in an RSV vaccine-enhanced inflammation model
Augmented sodium currents contribute to the enhanced excitability of small diameter capsaicin-sensitive sensory neurons isolated from Nf1+/⁻ mice
Loss of cystic fibrosis transmembrane conductance regulator function produces abnormalities in tracheal development in neonatal pigs and young children
Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²⁺ channel complex
Unidentified bright objects in neurofibromatosis type 1: conventional MRI in the follow-up and correlation of microstructural lesions on diffusion tensor images
Neurofibromatosis type 1 and cerebellar T2-hyperintensities: the relationship to cognitive functioning
Assessment of nociception and related quality-of-life measures in a porcine model of neurofibromatosis type 1.
Towards a neurobiological understanding of pain in neurofibromatosis type 1: mechanisms and implications for treatment
An executive functioning perspective in neurofibromatosis type 1: from ADHD and autism spectrum disorder to research domains.
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