Yu-Qiang Ding

M.D., Ph.D.
Head of Department
Tongji University · Anatomy and Neurobiology

Publications

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The canonical Wnt signaling pathway is critical for the development of midbrain dopaminergic (DA) neurons, and recent studies have suggested that disruption of this signaling cascade may underlie the pathogenesis of Parkinson's disease (PD). However, the exact role of the canonical Wnt signaling pathway, including low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) and β-catenin components, in a mouse model of PD remains unclear. In the present study, the tyrosine hydroxylase (TH)-Cre transgenic mouse line was used to generate mice with the specific knockout of LRP5, LRP6 or β-catenin in DA neurons. Following inactivation of LRP5, LRP6 or β-catenin, TH-immunohistochemical staining was performed. The results indicated that β-catenin is required for the development or maintenance of these neurons; however, LRP5 and LRP6 were found to be dispensable. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, the depletion of LRP5, LRP6 or β-catenin was found to be protective for the midbrain DA neurons to a certain extent. These in vivo results provide a novel perspective for the function of the canonical Wnt signaling pathway in a mouse model of PD.
    Experimental and therapeutic medicine 08/2014; 8(2):384-390. · 0.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates NADPH and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in mouse and cellular models of stroke, and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury.
    Journal of Neuroscience 05/2014; 34(22):7458-7471.. · 6.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During embryonic development of the mammalian cerebral cortex, postmitotic cortical neurons migrate radially from the ventricular zone to the cortical plate. Proper migration involves the correct orientation of migrating neurons and the transition from a multipolar to a mature bipolar morphology. Herein, we report that the 2 isoforms of Myosin-10 (Myo10) play distinct roles in the regulation of radial migration in the mouse cortex. We show that the full-length Myo10 (fMyo10) isoform is located in deeper layers of the cortex and is involved in establishing proper migration orientation. We also demonstrate that fMyo10-dependent orientation of radial migration is mediated at least in part by the netrin-1 receptor deleted in colorectal cancer. Moreover, we show that the headless Myo10 (hMyo10) isoform is required for the transition from multipolar to bipolar morphologies in the intermediate zone. Our study reveals divergent functions for the 2 Myo10 isoforms in controlling both the direction of migration and neuronal morphogenesis during radial cortical neuronal migration.
    Cerebral Cortex 05/2014; 24(5):1259-1268. · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Itch, chronic itch in particular, can have a significant negative impact on an individual's quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown. We report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine. Our results demonstrate a critical role for ERK activation in itch sensation at the spinal level.
    Molecular Brain 04/2014; 7(1):25. · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Renal regeneration approaches offer great potential for the treatment of chronic kidney disease, but their availability remains limited by the clinical challenges they pose. In the present study, we used continuous detergent perfusion to generate decellularized (DC) rat kidney scaffolds. The scaffolds retained intact vascular trees and overall architecture, along with significant concentrations of various cytokines, but lost all cellular components. To evaluate its potential in renal function recovery, DC scaffold tissue was grafted onto partially nephrectomized rat kidneys. An increase of renal size was found, and regenerated renal parenchyma cells were observed in the repair area containing the grafted scaffold. In addition, the number of nestin-positive renal progenitor cells was markedly higher in scaffold-grafted kidneys compared to controls. Moreover, radionuclide scan analysis showed significant recovery of renal functions at 6 weeks post-implantation. Our results provide further evidence to show that DC kidney scaffolds could be used to promote renal recovery in the treatment of chronic kidney disease.
    Biomaterials 01/2014; 35(25):6822–6828. · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several lines of evidence have suggested that the dysregulation of immune system is involved in the pathogenesis of schizophrenia. Microglia are the resident macrophage of the brain and the major player in innate immunity in the brain. We hypothesized that microglia activation may be closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (PD7), and they were separately treated with saline or minocycline for consecutive 3 days. Behavioral changes (locomotor activity, social interaction and prepulse inhibition) were examined in adulthood, and the number of microglia was assessed using immunohistochemistry at PD9, PD21 and PD67. The adult rats in LPS-injected group showed obvious behavioral alterations (deficits in social behavior and prepulse inhibition) and a persistently dramatic increase of number of activated microglial cells in the hippocampus, cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, pretreatment with minocycline could significantly rescue the behavioral deficits and prevent microglia activation. Our results suggest that neonatal intrahippocampal LPS injection may serve as a potential schizophrenia animal model, and inhibition of microglia activation may be a potential treatment strategy for schizophrenia.
    Brain Behavior and Immunity 01/2014; · 5.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia. Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (P7), and they were separately given saline, risperidone (0.5 mg/kg), minocycline (40 mg/kg) or a combination of both of them at P42 for consecutive 14 days. Behavioral changes (locomotion activity, social interaction, novel object recognition and prepulse inhibition) were examined and the number of microglia was assessed by using immunohistochemistry in adulthood. The adult rats in LPS-injected group showed obvious behavioral alteration (e. g. deficits in social interaction, novel object recognition and prepulse inhibition) and a dramatic increase of number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, application of either minocycline, risperidone or both of them significantly rescued behavioral deficits and attenuated microglia activation. Our results suggest that inhibition of microglia activation may be one of mechanisms underlying the antipsychotic effect of minocycline and risperidone.
    PLoS ONE 01/2014; 9(4):e93966. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex. Eliminating sensory input to either hemisphere by unilateral transection of infraorbital nerve (ION) prevents target selection of callosal axons in contralateral cortex. Strikingly, blocking sensory input bilaterally, by simultaneously transecting both IONs, results in rescued callosal projection. In contrast, non-simultaneous bilateral ION transection has the same effect as unilateral transection. Similar results are obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain slices treated with KCl is decreased more in contralateral cortex with unilateral removal of sensory input, but decreased similarly in both cortices in mice with simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical neurons is also reduced in contralateral cortex with the unilateral removal of sensory input, but equally reduced on both sides with the bilateral removal of sensory input, suggesting that unbalanced bilateral sensory input might lead to mismatched neuronal activity between the two cortices and contribute to the formation of callosal projection. Our data demonstrate a critical role of balanced bilateral somatosensory input in the formation of callosal connections, and thus reveal a new role of sensory input in wiring brain circuits.
    Molecular Brain 12/2013; 6(1):53. · 4.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serotonin-1A (5-HT1A) receptors modulate the stress response and have been implicated in the etiology and treatment of depression and anxiety disorders. A reduction in postsynaptic 5-HT1A receptor function in limbic areas has consistently been observed following exposure to chronic stress. To investigate the hypothesis that increased activation of 5-HT1A receptors in rats having reduced 5-HT function may improve stress adaptation and the behavioral sequelae commonly associated with chronic stress. One hundred forty-four Sprague-Dawley rats received injections of para-chlorophenylalanine to partially deplete 5-HT then were given daily systemic pretreatment with the 5-HT1A receptor agonist, 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT), the antagonist, WAY 100635, or vehicle prior to either restraint stress (6 h/day for 10 daily sessions) or control conditions. Anxiety- and depressive-like behaviors were then assessed using the open field and sucrose preference tests. Protein level of hippocampal glucocorticoid receptors (GR) and mineralocorticoid receptors was detected by immunohistochemistry and brain-derived neurotrophic factor (BDNF) was determined by in situ hybridization. 8-OH-DPAT pretreatment prior to stress exposure attenuated later stress-induced anxiety- and depression-like behaviors and increased GR and BDNF mRNA expression in the hippocampus relative to vehicle- and WAY 100635-pretreated, stressed animals. The stress-related impairments associated with 5-HT deficiency can be improved by 8-OH-DPAT pretreatment prior to stress exposure and are associated with an augmentation of GR-like immunoreactivity and BDNF mRNA expression in the hippocampus. It suggested that selective activation of 5-HT1A receptors may be a potential treatment strategy for stress-related disorders such as anxiety and depression.
    Psychopharmacology 11/2013; · 4.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our previous study identified a new form of spinocerebellar ataxia (SCA), in which mutations in the gene coding for transglutaminase 6 (TG6) were suggested to be causative. However, the data concerning cellular distribution of TG6 in the brain is still fragmentary. Therefore, we now report a comprehensive immunohistochemical examination of the expression profile of TG6 in adult mouse brain. TG6 was abundantly expressed in the septal region, basal ganglia, hypothalamus and brainstem. Notably, numerous TG6-positive neurons were found in the key brain regions involved in regulating locomotion activity, including the globus pallidus, subthalamic nucleus, substantia nigra, cerebellum, some precerebellar nuclei, and spinal motor neurons. Double immunostaining showed that the vast majority of TG6-positive neurons in the reticular nigra were GABAergic and those in the compact nigra were not dopaminergic. In addition, double staining for TG6 with either anti-NeuN or glial fibrillary acidic protein (GFAP) antibodies demonstrated exclusive NeuN-TG6 co-localization. This study presents a comprehensive overview of TG6 expression in the mouse brain, and provides insight for investigating the role of TG6 in the development of SCA. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 07/2013; · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in embryonic stem cells and neurons in mammals. However, its biological function in vivo is largely unknown. Here, we demonstrate that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain. Mice lacking Tet1 exhibit impaired hippocampal neurogenesis accompanied by poor learning and memory. In adult neural progenitor cells deficient in Tet1, a cohort of genes involved in progenitor proliferation were hypermethylated and downregulated. Our results indicate that Tet1 is positively involved in the epigenetic regulation of neural progenitor cell proliferation in the adult brain.
    Cell stem cell 06/2013; · 23.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole-brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting-state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole-brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph-theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal-limbic-thalamic-cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole-brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 02/2013; · 6.88 Impact Factor
  • Source
    Ying Huang, Ning-Ning Song, Wei Lan, Ling Hu, Chang-Jun Su, Yu-Qiang Ding, Lei Zhang
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous investigations on the expression and function of special AT-rich sequence binding protein 2 (Satb2) are largely limited to the cerebral cortex. Here, we explore the expression of Satb2 thoroughly by immunohistochemistry in the adult mouse central nervous system (CNS). Besides the cerebral cortex, we found that Satb2 is specifically expressed in the bed nucleus of the stria terminalis, horizontal limb of the diagonal band, lateral hypothalamic area, arcuate nucleus, hypothalamic paraventricular nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, dorsal raphe nucleus, rostral periolivary region, and parabrachial nucleus. Double immunostaining showed that Satb2 is exclusively expressed in the excitatory neurons of neocortex. In addition, Satb2 is specifically expressed in A12 group of hypothalamic dopaminergic neurons and in serotonergic neurons in the dorsal part of the dorsal raphe nucleus. Our results present a comprehensive overview of Satb2 expression in the adult brain and provide insights for studying the role of Satb2 in the mature CNS. Anat Rec, 2013. © 2013 Wiley Periodicals, Inc.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 02/2013; · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures. Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed. Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma. The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.
    PLoS ONE 01/2013; 8(7):e69350. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Somatosensory ganglia including dorsal root ganglion (DRG) and trigeminal ganglion (TG) are derived from a common pool of neural crest stem cells (NCCs), and are good systems to study the mechanisms of neurogenesis and gliogenesis. Previous studies have reported that deletion of Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells resulted in the delayed gliogenesis at early stage and a loss of glial cells at later stage in the DRG. But the phenotypes in the TG have not been described. Here we reported although the gliogenesis was also delayed initially in Rbpj-deficient TG, it was recovered as the development progressed, as shown by the presence of large number of glial cells in the TG at later stages. However, neuronal reduction was observed in Rbpj-deficient TG, which is similar to what observed in Rbpj-deficient DRG. Taken together, our data indicate the function of Rbpj is diversified and context dependent in the gliogenesis of somatosensory ganglia.
    International journal of clinical and experimental pathology 01/2013; 6(7):1261-71. · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous investigations on the expression and function of special AT‐rich sequence binding protein 2 (Satb2) are largely limited to the cerebral cortex. Here, we explore the expression of Satb2 thoroughly by immunohistochemistry in the adult mouse central nervous system (CNS). Besides the cerebral cortex, we found that Satb2 is specifically expressed in the bed nucleus of the stria terminalis, horizontal limb of the diagonal band, lateral hypothalamic area, arcuate nucleus, hypothalamic paraventricular nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, dorsal raphe nucleus, rostral periolivary region, and parabrachial nucleus. Double immunostaining showed that Satb2 is exclusively expressed in the excitatory neurons of neocortex. In addition, Satb2 is specifically expressed in A12 group of hypothalamic dopaminergic neurons and in serotonergic neurons in the dorsal part of the dorsal raphe nucleus. Our results present a comprehensive overview of Satb2 expression in the adult brain and provide insights for studying the role of Satb2 in the mature CNS. Anat Rec, 296:452–461, 2013. © 2013 Wiley Periodicals, Inc.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 01/2013; 296(3). · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Key points  Zinc finger and BTB domain-containing protein 20 (Zbtb20) plays a critical role in hippocampal development.  In the present study, we generated mutant mice in which Zbtb20 knockout was restricted to mature CA1 pyramidal cells of the hippocampus.  Conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired LTP and memory.  We found that Zbtb20 controls memory formation and synaptic plasticity by regulating NMDAR activity, and activation of ERK and CREB.
    The Journal of Physiology 07/2012; 590(Pt 19):4917-32. · 4.38 Impact Factor
  • Source
    Ming Shi, Ze-Lan Hu, Min-Hua Zheng, Ning-Ning Song, Ying Huang, Gang Zhao, Hua Han, Yu-Qiang Ding
    [Show abstract] [Hide abstract]
    ABSTRACT: The locus coeruleus (LC) is the main source of noradrenaline in the brain and is implicated in a broad spectrum of physiological and behavioral processes. However, genetic pathways controlling the development of noradrenergic neurons in the mammalian brain are largely unknown. We report here that Rbpj, a key nuclear effector in Notch signaling pathway, plays an essential role in the LC neuron development in the mouse. Conditional inactivation of Rbpj in the dorsal rhombomere (r) 1, where LC neurons are born, resulted in a dramatic increase in the number of Phox2a- and Phox2b-expressing early-differentiating LC neurons, and dopamine-β-hydroxylase- and tyrosine hydroxylase-expressing late-differentiating LC neurons. In contrast, other neuronal populations derived from the dorsal r1 were either reduced or unchanged. In addition, a drastic upregulation of Ascl1, an essential factor for noradrenergic neurogenesis, was observed in the dorsal r1 of the conditional knockout mice. Through genomic sequence analysis and EMSA and ChIP assays, a conserved Rbpj-binding motif was identified within the Ascl1 promoter. Luciferase reporter assay revealed that Rbpj per se could induce Ascl1 transactivation but this effect was counteracted by its downstream-targeted gene Hes1. Moreover, our in vitro gene transfection and in ovo electroporation assays showed that Rbpj upregulated Ascl1 expression when Hes1 expression was knocked down, though it also exerted a repressive effect on Ascl1 expression in the presence of Hes1. Thus, our results provide the first evidence that Rbpj functions as a key modulator of LC neuron development via regulating Ascl1 expression in a direct manner and as well as via an indirect way mediated by its targeted gene Hes1.
    Journal of Cell Science 06/2012; · 5.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prrxl1-CreER(T2) transgenic mice expressing tamoxifen-inducible Cre recombinase were generated by modifying a Prrxl1-containing BAC clone. Cre recombination activity was examined in Prrxl1-CreER(T2); Rosa26 reporter mice at various embryonic and postnatal stages. Pregnant mice were treated with a single dose of tamoxifen at embryonic day (E) 9.5 or E12.5, and X-gal staining was performed 2 days later. Strong X-gal staining was observed in the somatosensory ganglia (e.g., dorsal root and trigeminal ganglia) and the first central sites for processing somatosensory information (e.g., spinal dorsal horn and trigeminal nerve-associated nuclei). When tamoxifen was administered at postnatal day (P) 20 or in adulthood (P120), strong Cre recombination activity was present in the primary somatosensory ganglia, while weak Cre recombination activity was found in the spinal dorsal horn, mesencephalic trigeminal nucleus, principal sensory trigeminal nucleus, and spinal trigeminal nucleus. This mouse line provides a useful tool for exploring genes' functions in the somatosensory system in a time-controlled way.
    genesis 02/2012; 50(7):552-60. · 2.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis.
    PLoS ONE 01/2012; 7(10):e47358. · 3.53 Impact Factor

24 Following View all

64 Followers View all