21 research outputs found

    MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

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    Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase (www.facebase.org, https://doi.org/10.25550/3-HXMC) and GitHub (https://github.com/jaydevine/MusMorph)

    MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses.

    Get PDF
    Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase ( www.facebase.org , https://doi.org/10.25550/3-HXMC ) and GitHub ( https://github.com/jaydevine/MusMorph )

    Soluble Nogo66 receptor promotes retinal ganglion cell survival after optic nerve transection and ocular hypertension-induced glaucoma injuries

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    Three myelin proteins bind to the neuronal Nogo66 receptor (NgR1) that mediates the inhibition of axonal regeneration possibly via two transmembrane coreceptors, LINGO-1 and p75/TROY in the central nervous system (CNS). Modulation of the interactions of these myelin inhibitory proteins with NgR1 can overcome the inhibitory effects of CNS myelin in vitro and in vivo in models of spinal cord injuries. In addition to previous studies that have focused on the roles of NgR1 antagonists in promoting axonal regeneration, here we examined the effect of a soluble fragment of NgR1, sNgR1(27-310)-Fc fusion protein, when injected intravitrealy immediately after injury, on retinal ganglion cell (RGC) survival after ocular hypertension (chronic injury) and optic nerve transection (acute injury). The results showed that sNgR1(27-310)-Fc significantly reduced the loss of RGCs in the ocular hypertension glaucoma model 2 weeks after injury and promoted the survival of RGCs 7 days after optic nerve transection. Thus, sNgR1(27-310)-Fc may exhibit neuroprotective activity in addition to its NgR1 antagonist activity that promotes CNS axonal regeneration. Corresponding authors: KF So and DHS Lee. Supported by Biogen Idec Inc

    The anti-NgR1 antibody, 1D9, rescues rat retinal ganglion cells after optic nerve transection and ocular hypertension-induced glaucoma

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    The neuronal leucine rich repeat protein, Nogo66 receptor [NgR1], interacts with at least three CNS myelin proteins [Nogo, MAG and OMgp] and mediates the inhibition of neurite growth. Here we report a monoclonal anti-NgR1 antibody, 1D9, that in addition to inhibiting these interactions in vitro, exhibits neuroprotective properties in vitro and in vivo. Structural analyses performed on the co-crystal complex of the 1D9 Fab and a soluble fragment of NgR1 (sNgR310) indicate that this antibody binds near the junction of the N-terminus cap and leucine rich repeat domain on NgR1. Treatment with 1D9 protected primary neuronal cultures from insults derived from serum withdrawal. Direct intravitreal administration of 1D9 Fab, but not the full 1D9 mAb, consistently promoted the survival of retinal ganglion cells in an optic nerve transection model and an ocular hypertension induced glaucoma model in rat. The lack of activity of the full 1D9 mAb may be partially attributed to NgR1 activation via receptor cross-linking as demonstrated by rhoA activation assay. These results suggest that 1D9 Fab may confer neuroprotection to specific subsets of neurons. Equal contribution: B Hu, A Jirik, and Q Fu Corresponding authors: KF So and DHS Le

    Antigen-Induced Pten Gene Deletion in T Cells Exacerbates Neuropathology in Experimental Autoimmune Encephalomyelitis

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    The Pten tumor suppressor gene is critical for normal intrathymic development of T cells; however, its role in mature antigen-activated T cells is less well defined. A genetically crossed mouse line, Ptenfl/fl GBC, in which Pten gene deletions could be primarily confined to antigen-activated CD8+ T cells, enabled us to evaluate the consequences of Pten loss on the course of experimental autoimmune encephalomyelitis. Compared with Ptenfl/fl controls, myelin oligodendrocyte glycoprotein (MOG) peptide-immunized Ptenfl/fl GBC mice developed more severe and protracted disease. This was accompanied by increased spinal cord white matter myelin basic protein depletion and axonal damage, as well as a striking persistence of macrophage and granzyme B-expressing cellular neuroinfiltrates in the chronic phase of the disease. This persistence may be explained by the observation that anti-CD3 activated Ptenfl/fl GBC T cells were more resistant to proapoptotic stimuli. Consistent with the predicted consequences of Pten loss, purified CD8+ T cells from Ptenfl/fl GBC mice displayed augmented proliferative responses to anti-T-cell receptor stimulation, and MOG-primed Ptenfl/fl GBC T cells exhibited a reduced activation threshold to MOG peptide. Ptenfl/fl GBC mice also developed atypical central nervous system disease, manifested by prominent cervical cord and forebrain involvement. Collectively, our findings indicate that the phosphatidylinositol 3-kinase signaling pathway is an essential regulator of CD8+ T-cell effector function in experimental autoimmune encephalomyelitis
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