Omkar L. Patkar
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View article: Correction: Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis and inflammation
Correction: Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis and inflammation Open
Characterization of a novel IL34 loss-of-function model reveals overlapping functions of CSF1 and IL34 on CSF1R in the brain and periphery of the rat.
View article: Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation
Mutation in the rat interleukin 34 gene impacts macrophage development, homeostasis, and inflammation Open
Interleukin 34 (IL34) and colony-stimulating factor 1 (CSF1) signal through a shared receptor (CSF1R) to control macrophage survival, differentiation, and function. Here, we describe the impact of loss-of-function mutation in the rat Il34 …
View article: Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation
Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation Open
Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the colony-stimulating factor 1 receptor ( Csf1r) gene ( Csf1rko ) severely compromises pre-w…
View article: Repopulation of the brain with microglia-like cells following intraperitoneal bone marrow cell transfer in microglia-deficient mice
Repopulation of the brain with microglia-like cells following intraperitoneal bone marrow cell transfer in microglia-deficient mice Open
Germ-line deletion of a conserved enhancer (the Fms intrinsic regulatory element, FIRE) in the mouse Csf1r locus causes congenital absence of microglia. Homozygous FIRE deletion on a C57BL/6J background leads to perinatal lethality and hyd…
View article: Biallelic SLC13A1 loss-of-function variants result in impaired sulfate transport and skeletal phenotypes, including short stature, scoliosis, and skeletal dysplasia
Biallelic SLC13A1 loss-of-function variants result in impaired sulfate transport and skeletal phenotypes, including short stature, scoliosis, and skeletal dysplasia Open
Biallelic loss-of-function variants in SLC13A1 are a novel cause of skeletal phenotypes in humans with a measurable biomarker. Sulfate measurements should be considered in the clinical interpretation of variants identified in SLC13A1.
View article: An Inactivating Mutation in Rat IL-34 Reveals Redundant and Nonredundant Functions of CSF1-IL-34 Signalling in Homeostasis and Inflammation
An Inactivating Mutation in Rat IL-34 Reveals Redundant and Nonredundant Functions of CSF1-IL-34 Signalling in Homeostasis and Inflammation Open
Colony stimulating factor 1 receptor (CSF1R) is required for the differentiation and maintenance of many mononuclear phagocyte lineage cells and is a definitive marker of this lineage in humans and mice. CSF1R signaling is activated by two…
View article: Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation
Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation Open
Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the Csf1r gene ( Csf1rko ) severely compromises pre-weaning somatic growth and maturation of …
View article: Relative contributions of osteal macrophages and osteoclasts to postnatal bone development in CSF1R-deficient rats and phenotype rescue following wild-type bone marrow cell transfer
Relative contributions of osteal macrophages and osteoclasts to postnatal bone development in CSF1R-deficient rats and phenotype rescue following wild-type bone marrow cell transfer Open
Macrophage and osteoclast proliferation, differentiation and survival are regulated by colony-stimulating factor 1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 and Csf1r mutations has been attributed to the loss of osteoc…
View article: Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism
Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism Open
CSF1 administration expands tissue macrophages, which transforms systemic metabolism. CSF1 drives fat mobilization and glucose uptake to support liver growth. The effects of CSF1 are independent of normal hormonal metabolic regulation. The…
View article: Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic metabolism to fuel liver growth
Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic metabolism to fuel liver growth Open
Background and Aim Macrophages regulate metabolic homeostasis in health and disease. Macrophage colony-stimulating factor (CSF1)-dependent macrophages contribute to homeostatic control of the size of the liver. This study aimed to determin…
View article: Intraperitoneal transfer of wild‐type bone marrow repopulates tissue macrophages in the <i>Csf1r</i> knockout rat without contributing to monocytopoiesis
Intraperitoneal transfer of wild‐type bone marrow repopulates tissue macrophages in the <i>Csf1r</i> knockout rat without contributing to monocytopoiesis Open
Homozygous null mutation of the Csf1r gene ( Csf1rko ) in rats leads to the loss of most tissue macrophage populations and pleiotropic impacts on postnatal growth and organ maturation, leading to early mortality. The phenotype can be rever…
View article: Intraperitoneal transfer of wild-type bone marrow cells in the<i>Csf1r</i>knockout rat repopulates resident tissue macrophages without contributing to monocytopoiesis
Intraperitoneal transfer of wild-type bone marrow cells in the<i>Csf1r</i>knockout rat repopulates resident tissue macrophages without contributing to monocytopoiesis Open
Homozygous null mutation of the macrophage colony-stimulating factor receptor ( Csf1r ) gene in rats leads to the loss of most tissue macrophage populations and has pleiotropic impacts on postnatal growth and organ maturation leading to mo…
View article: A kinase-dead <i>Csf1r</i> mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signalling
A kinase-dead <i>Csf1r</i> mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signalling Open
Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-…
View article: Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease
Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease Open
Resident and recruited macrophages control the development and proliferation of the liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyt…
View article: Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease
Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease Open
Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte pr…
View article: A kinase-dead <i>Csf1r</i> mutation associated with adult-onset leukoencephalopathy has a dominant-negative impact on CSF1R signaling
A kinase-dead <i>Csf1r</i> mutation associated with adult-onset leukoencephalopathy has a dominant-negative impact on CSF1R signaling Open
Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-…
View article: CSF1R-dependent macrophages control postnatal somatic growth and organ maturation
CSF1R-dependent macrophages control postnatal somatic growth and organ maturation Open
Homozygous mutation of the Csf1r locus ( Csf1rko ) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Cs…
View article: A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity
A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity Open
While the dire cardiometabolic consequences of the hypercaloric modern ‘Western’ diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that r…
View article: Analysis of homozygous and heterozygous Csf1r knockout in the rat as a model for understanding microglial function in brain development and the impacts of human CSF1R mutations
Analysis of homozygous and heterozygous Csf1r knockout in the rat as a model for understanding microglial function in brain development and the impacts of human CSF1R mutations Open
Mutations in the human CSF1R gene have been associated with dominant and recessive forms of neurodegenerative disease. Here we describe the impacts of Csf1r mutation in the rat on development of the brain. Diffusion imaging indicated small…
View article: CSF1R-dependent macrophages control postnatal somatic growth and organ maturation
CSF1R-dependent macrophages control postnatal somatic growth and organ maturation Open
Homozygous mutation of the Csf1r locus ( Csf1rko ) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Cs…
View article: Pindolol Rescues Anxiety-Like Behavior and Neurogenic Maladaptations of Long-Term Binge Alcohol Intake in Mice
Pindolol Rescues Anxiety-Like Behavior and Neurogenic Maladaptations of Long-Term Binge Alcohol Intake in Mice Open
Long-term binge alcohol consumption alters the signaling of numerous neurotransmitters in the brain including noradrenaline (NE) and serotonin (5-HT). Alterations in the signaling of these neuronal pathways result in dysfunctional emotiona…
View article: Axonal Non-segregation of the Vesicular Glutamate Transporter VGLUT3 Within Serotonergic Projections in the Mouse Forebrain
Axonal Non-segregation of the Vesicular Glutamate Transporter VGLUT3 Within Serotonergic Projections in the Mouse Forebrain Open
A subpopulation of raphe 5-HT neurons expresses the vesicular glutamate transporter VGLUT3 with the co-release of glutamate and serotonin proposed to play a pivotal role in encoding reward- and anxiety-related behaviors. Serotonin axons ar…
View article: Sifting through the surfeit of neuroinflammation tracers
Sifting through the surfeit of neuroinflammation tracers Open
The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [ 11 C]-( R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) …
View article: Binge-like sucrose consumption reduces the dendritic length and complexity of principal neurons in the adolescent rat basolateral amygdala
Binge-like sucrose consumption reduces the dendritic length and complexity of principal neurons in the adolescent rat basolateral amygdala Open
A compelling body of evidence suggests that the worldwide obesity epidemic is underpinned by excessive sugar consumption, typified by the modern western diet. Furthermore, evidence is beginning to emerge of maladaptive changes in the mesol…
View article: Serotonin and Noradrenaline Signalling in Binge-Like Long-Term Alcohol Intake and Associated Maladaptive Effects in Adult Mice
Serotonin and Noradrenaline Signalling in Binge-Like Long-Term Alcohol Intake and Associated Maladaptive Effects in Adult Mice Open
Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. This thesis investigated the contribution of two key neurotransmitters; noradrenaline and serotonin in alcohol dependence u…