An essential step in researching human central nervous system (CNS) disorders is the search for appropriate mouse models that can be used to investigate both genetic and environmental factors underlying the etiology of such conditions. Identification of murine models relies upon detailed pre- and post-natal phenotyping since profound defects are not only the result of gross malformations but can be the result of small or subtle morphological abnormalities. The difficulties in identifying such defects are compounded by the finding that many mouse lines show quite a variable penetrance of phenotypes. As a result, without analysis of large numbers, such phenotypes are easily missed. Indeed for null mutations, around one-third have proved to be pre- or perinatally lethal, their analysis resting entirely upon phenotyping of accessible embryonic stages.To simplify the identification of potentially useful mouse mutants, we have conducted three-dimensional phenotype analysis of approximately 500 homozygous null mutant embryos, produced from targeting a variety of mouse genes and harvested at embryonic day 14.5 as part of the "Deciphering the Mechanisms of Developmental Disorders" www.dmdd.org.uk program. We have searched for anatomical features that have the potential to serve as biomarkers for CNS defects in such genetically modified lines. Our analysis identified two promising biomarker candidates. Hypoglossal nerve (HGN) abnormalities (absent, thin, and abnormal topology) and abnormal morphology or topology of head arteries are both frequently associated with the full spectrum of morphological CNS defects, ranging from exencephaly to more subtle defects such as abnormal nerve cell migration. Statistical analysis confirmed that HGN abnormalities (especially those scored absent or thin) indeed showed a significant correlation with CNS defect phenotypes. These results demonstrate that null mutant lines showing HGN abnormalities are also highly likely to produce CNS defects whose identification may be difficult as a result of morphological subtlety or low genetic penetrance.
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http://dx.doi.org/10.3389/fnana.2021.625716 | DOI Listing |
Audiol Res
December 2024
ENT & Audiology Unit, Department of Neurosciences, University Hospital of Ferrara, 44124 Ferrara, Italy.
Objectives: The present study aims to identify potential predictive factors for developing sensorineural hearing loss (SNHL) in individuals with congenital Cytomegalovirus (cCMV) infection.
Methods: A retrospective study was performed on 50 subjects with cCMV infection (symptomatic and asymptomatic), followed at the Audiology Service of Sant'Anna Hospital (University Hospital of Ferrara). The following data were analyzed: the type of maternal Cytomegalovirus (CMV) infection (primary versus non-primary), time of in utero infection, systemic signs and symptoms or laboratory test anomalies due to cCMV infection, and signs and symptoms of central nervous system (CNS) involvement at birth.
Clin Rheumatol
January 2025
Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey.
Monogenic lupus is an extremely rare clinical condition in children. Defects in the complement pathway are the most common causes of monogenic lupus. C1qC deficiency is one of the defects in this pathway and is even rarer.
View Article and Find Full Text PDFMol Genet Metab
January 2025
Division of Medical Genetics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is an X-linked lysosomal storage disorder. It results from a deficiency of the enzyme iduronate-2-sulfatase (I2S), leading to the accumulation of glycosaminoglycans (GAGs) in various tissues and organs. Clinical manifestations include skeletal abnormalities, facial coarsening, organ enlargement, and developmental delays.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Department of Biological Sciences, Middle East Technical University, Ankara, Türkiye.
Primary familial brain calcification (PFBC) is a rare, progressive central nervous system (CNS) disorder without a cure, and the current treatment methodologies primarily aim to relieve neurological and psychiatric symptoms of the patients. The disease is characterized by abnormal bilateral calcifications in the brain, however, our mechanistic understanding of the biology of the disease is still limited. Determining the roles of the specific cell types and molecular mechanisms involved in the pathophysiological processes of the disease is of great importance for the development of novel and effective treatment methodologies.
View Article and Find Full Text PDFPurinergic Signal
January 2025
Department of Biology, Faculty of Science, University of British Columbia Okanagan Campus, Kelowna, BC, V1V 1V7, Canada.
The two main glial cell types of the central nervous system (CNS), astrocytes and microglia, are responsible for neuroimmune homeostasis. Recent evidence indicates astrocytes can participate in removal of pathological structures by becoming phagocytic under conditions of neurodegenerative disease when microglia, the professional phagocytes, are impaired. We hypothesized that adenosine triphosphate (ATP), which acts as damage-associated molecular pattern (DAMP), when released at high concentrations into extracellular space, upregulates phagocytic activity of human astrocytes.
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