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Hardgrave, A.

Publications and source records attributed to Hardgrave, A..

2 recordsLinked to original sources

The Preclinical Animal Network (PCAN): Integrative high-throughput phenotyping of standardized mouse models for Prader-Willi syndrome

The Preclinical Animal Network (PCAN) is a collaborative resource established to advance translational research and therapeutic development for Prader-Willi syndrome (PWS), a rare neurodevelopmental disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. PCAN integrates standardized, high-throughput phenotyping of approximately 1,000 mice across six engineered lines carrying paternal deletions of Ndn, Magel2, Snord116, Ipw, and multigenic loci. Using validated experimental pipelines spanning metabolic, behavioral, and developmental domains, we captured comprehensive phenotypic profiles by applying a statistical variance-decomposition framework to partition genetic and environmental contributions. This analysis provides robust genotype-phenotype maps, revealing shared and model-specific phenotypic effects while accounting for key confounding factors. The PCAN resource provides a framework for evaluating PWS-relevant phenotypes and benchmarking therapeutic strategies. By providing open access to its mouse models, datasets and analytical resources, PCAN enables the research community to apply standardized, reproducible workflows and accelerate the development of targeted, mechanism-based treatments.

genetics↗

Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominated by auto-antibodies that recognise cellular components. Pleural involvement is the most common SLE-related lung disease. Natural antibodies are rapidly secreted by innate-like B cells following perturbation of homeostasis and are important in the early stages of immune activation. The serous cavities are home to large numbers of innate-like B cells present both within serous fluid and resident within fat-associated lymphoid clusters (FALCs). FALCs are important hubs for B-cell activation and local antibody secretion within the body cavities. Patients with SLE can develop anti-phospholipid antibodies and in rare situations develop alveolar haemorrhage. Utilising delivery of the hydrocarbon oil pristane in C57BL/6 mice as a model of SLE we identify a rapid expansion of pleural cavity B cells as early as day 3 after intra-peritoneal pristane delivery. Following pristane delivery, pericardial B1 B cells are proliferative, express the plasma-cell surface marker CD138 and secrete both innate and class switched antibodies highlighting that this cavity niche may play an unrecognised role in the initiation of lupus pleuritis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/549766v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@18ea5bforg.highwire.dtl.DTLVardef@23d9deorg.highwire.dtl.DTLVardef@1b48b3aorg.highwire.dtl.DTLVardef@20a133_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗