To improve the efficiency of gene disruption in Stagonospora nodorum, the putative KU70 gene encoding the Ku70 protein involved in the nonhomologous end-joining double DNA break repair pathway was identified and deleted. The KU70 disruption strain showed no apparent defect in vegetable growth, conidiation and pathogenicity on wheat and barley compared with the wild-type strain. The effect of the absence of KU70 on gene replacement frequency was tested by disruption of TOXA encoding toxin A and LIP2 encoding a putative lipase. Frequency of gene replacement for both genes was dramatically increased in the KU70 disruption strain, compared with the low frequency in the wild-type recipient.
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http://dx.doi.org/10.1016/j.micres.2011.05.004 | DOI Listing |
Calcif Tissue Int
January 2025
Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Santa Maria Alle Scotte, Siena, Italy.
Aromatase deficiency (ORPHA:91; OMIM: 613,546) is a rare, autosomal recessive disorder due to loss of function mutations in the CYP19A1 gene, described in both genders with an estimated incidence below 1/1000000. While in female the clinical manifestations generally occur at birth or in early infancy, and mainly involve sexual characteristics, in men clinical signs of aromatase deficiency mostly occur in puberty and especially in late puberty, so that diagnosis is generally established after the second decade due to tall stature, unfused epiphyses and reduced bone mass. Here we review the available information concerning the skeletal and extraskeletal phenotype and the clinical management of bone health in patients with aromatase CYP19A1 gene mutations.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
German Center for Neurodegenerative Diseases (DZNE), Munich, Bavaria, Germany.
Background: Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-GRN). Multiple therapeutic strategies are in clinical development to restore PGRN levels in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: Common and rare variants in SORL1 have been associated with increased risk of Alzheimer's disease (AD). Since 2019, we have run an international collaborative research initiative to ascertain a Peruvian cohort for Alzheimer's disease and other related dementias for genetic studies (PeADI).
Method: A Peruvian family (4 AD cases and two mild cognitive impairment (MCI) cases) was recruited through the PeADI study.
Alzheimers Dement
December 2024
Institute for Memory Impairments and Neurological Disorders (MIND), Irvine, CA, USA.
Background: Late-onset Alzheimer's disease (LOAD) represents the majority of human AD cases, yet the availability of animal models that accurately reflect LOAD progression and pathology is limited. Traditional transgenic mouse models including 3xTg-AD and 5xFAD rely on supraphysiological overexpression of familial AD risk genes, failing to adequately replicate the disease progression observed in LOAD. Here, we present the first characterization of MODEL-AD1 (MAD1), a platform mouse developed by the Model Organism Development and Evaluation for Late-onset Alzheimer's Disease (MODEL-AD) Consortium.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Arizona, Tucson, AZ, USA.
Background: Research into Alzheimer's Disease (AD) pathomechanisms frequently utilizes animal models with dominant mutations; however, the vast majority (>95%) of AD cases are idiopathic. Animal models with AD risk factors represent an approach with potentially greater translational validity. The predominant genetic risk factor for AD is the Apolipoprotein E ε4 (APOE4) polymorphism, with APOE4 homozygosity conferring approximately 15-fold higher risk relative to the normative APOE3/3 genotype.
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