Publications by authors named "A R Isles"

Article Synopsis
  • Loss of function mutations in the SETD1A gene are linked to various neurodevelopmental disorders, particularly schizophrenia, prompting research using a mouse model with Setd1a haploinsufficiency.
  • The study revealed sex-related differences in development and behavior, with male mice showing lower body weights and enhanced growth, while both sexes exhibited increased anxiety-like behaviors and impaired pre-pulse inhibition relevant to schizophrenia.
  • Additionally, the response to common antipsychotic medications varied, indicating that Setd1a haploinsufficient mice could serve as a useful model for understanding schizophrenia's biological basis and the underlying neural mechanisms that may differ by sex.
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Introduction: Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important.

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The MRC National Mouse Genetics Network (NMGN) has been established in the UK to bring together researchers from academia and industry across the country from a wide range of disease areas and research backgrounds to rapidly facilitate clinical translation of mouse research findings and foster an environment of interdisciplinary learning.

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Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations responsible for controlling parental care, to test whether imprinted genes significantly converge to regulate parenting behaviour.

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Genomic imprinting refers to the parent-of-origin expression of genes, which originates from epigenetic events in the mammalian germ line. The evolution of imprinting may reflect a conflict over resource allocation early in life, with silencing of paternal genes in offspring soliciting increased maternal provision and silencing of maternal genes limiting demands on the mother. Parental caregiving has been identified as an area of potential conflict, with several imprinted genes serendipitously found to directly influence the quality of maternal care.

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