To generate conditional gene knockouts in osteoblasts, we previously developed transgenic mice in which Cre recombinase cDNA was cloned downstream of a 3.6 or 2.3 kb fragment of the rat Col1a1 promoter (Col3.6-Cre and Col2.3-Cre, respectively). Col-Cre mice were bred with mice in which exon 4 of the Igf1 gene is flanked by loxP sites. Mating units were arranged such that either the male or the female breeder transmitted the Col-Cre transgenes. Progeny were evaluated for Cre-mediated Igf1 gene rearrangement. We found that the loxP-flanked Igf1 locus was rearranged in the absence of inheritance of the Cre transgene. The incidence was 50 and 28% with Col2.3-Cre and Col3.6-Cre females, respectively, and 15 and 18% with Col2.3-Cre and Col3.6-Cre males, respectively.
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http://dx.doi.org/10.1002/dvg.20259 | DOI Listing |
Epilepsia Open
December 2024
Integrated Diagnostics for Epilepsy, Department of Diagnostic and Technology, European Reference Network EPIcare, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Neuronal ceroid lipofuscinoses (NCLs) are genetically heterogeneous neurodegenerative disorders, characterized by progressive cognitive and motor decline, epilepsy, visual impairment, and shortened life-expectancy. CLN6-related NCLs include both late-infantile and adult myoclonic form. We report a 21-year-old patient, with mild developmental delay, who developed occipital seizures at 14 years, and subsequently cognitive decline, cortical myoclonus, and photosensitivity at low and higher frequencies.
View Article and Find Full Text PDFHereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder with manifestations including severe nose bleeding and microhemorrhage in brains. Despite being the second most common inherited bleeding disorder, the pathophysiological mechanism underlying HHT-associated hemorrhage is poorly understood. HHT pathogenesis is thought to follow a Knudsonian two-hit model, requiring a second somatic mutation for lesion formation.
View Article and Find Full Text PDFThe Wnt1-Cre2 driver, designed to address the effect of Wnt1 overactivation in the ventral neural tube in the original Wnt1-Cre line, was recently shown to have ectopic expression in the male germline. When crossed with a reporter mouse, we observed fluorescent protein expression in non-neural-crest cell types in the gut. Here, we characterize the pattern of Cre-mediated recombination in the Wnt1-Cre2 driver using three transgenic reporter lines.
View Article and Find Full Text PDFDeleterious germline variants constitute the most common inherited predisposition disorder linked to myeloid neoplasms (MNs). The role of DDX41 in hematopoiesis and how its germline and somatic mutations contribute to MNs remain unclear. Here we show that DDX41 is essential for erythropoiesis but dispensable for the development of other hematopoietic lineages.
View Article and Find Full Text PDFBone Res
October 2024
Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Diseases, Shanghai Jiao Tong University of Medicine Affiliated Sixth People's Hospital, Shanghai, China.
Cellular communication network factor 2 (CCN2) is a secreted extracellular matrix-associated protein, and its aberrantly increased expression has been implicated in a diversity of diseases involving pathological processes of fibrosis, chronic inflammation, or tissue injury, which has promoted the evaluation of CCN2 as therapeutic targets for multiple disorders. However, human phenotypes associated with CCN2 deficiency have remained enigmatic; variants in CCN2 have not yet been associated with a human phenotype. Here, we collected families diagnosed with spondyloepimetaphyseal dysplasia (SEMD), and screened candidate pathogenic genes for families without known genetic causes using next-generation sequencing.
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