Suckling defect in mice lacking the soluble haemopoietin receptor NR6

Ws, Alexander; Rakar, Steven; Robb, Lorraine; Farley, Alison; Ta, Willson; Jg, Zhang; Hartley, Lynne; Kikuchi, Yukiko; Kojima, Tetsuo; Nomura, Hitoshi; Hasegawa, Masakazu; Maeda, Masatsugu; Fabri, Louis; Jachno, Kim; Nash, Andrew D.; Metcalf, Donald; Nicola, Nicos A.; Hilton, Douglas J.

doi:10.1016/s0960-9822(99)80266-8

Cited by 71 publications

(78 citation statements)

References 10 publications

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“…Although the signaling cascade resulting from the binding to the receptor is already well defined (Lelievre et al, 2001), the role of the CLF-1 factor in terms of cellular responses has not yet been investigated. Until now, the only information available comes from the CLF-1 À/À mice that have reduced numbers of hemopoietic progenitor cells, fail to suckle and die within 24 h after birth (Alexander et al, 1999). Whole mount in situ hybridization reveals CLF-1 expression at several sites in the developing embryo and notably in the secretory buds and ducts of the submandibular salivary glands at 14.5 and 18.5 dpc (Alexander et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Until now, the only information available comes from the CLF-1 À/À mice that have reduced numbers of hemopoietic progenitor cells, fail to suckle and die within 24 h after birth (Alexander et al, 1999). Whole mount in situ hybridization reveals CLF-1 expression at several sites in the developing embryo and notably in the secretory buds and ducts of the submandibular salivary glands at 14.5 and 18.5 dpc (Alexander et al, 1999). This brings the hypothesis that PLAG1 could be one of the regulators of CLF-1 expression in the developing salivary gland, controlling the salivary gland organogenesis via this cytokine.…”

Section: Discussionmentioning

confidence: 99%

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Microarray screening for target genes of the proto-oncogene PLAG1

et al. 2004

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PLAG1 is a proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary glands and of lipoblastomas. As PLAG1 is a transcription factor, able to activate transcription through the binding to the consensus sequence GRGGC(N) 6-8 GGG, its ectopic expression presumably results in the deregulation of target genes, leading to uncontrolled cell proliferation. The identification of PLAG1 target genes is therefore a crucial step in understanding the molecular mechanisms involved in PLAG1-induced tumorigenesis. To this end, we analysed the changes in gene expression caused by the conditional induction of PLAG1 expression in fetal kidney 293 cell lines. Using oligonucleotide microarray analyses of about 12 000 genes, we consistently identified 47 genes induced and 12 genes repressed by PLAG1. One of the largest classes identified as upregulated PLAG1 targets consists of growth factors such as the insulin-like growth factor II and the cytokinelike factor 1. The in silico search for PLAG1 consensus sequences in the promoter of the upregulated genes reveals that a large proportion of them harbor several copies of the PLAG1-binding motif, suggesting that they represent direct PLAG1 targets. Our approach was complemented by the comparison of the expression profiles of pleomorphic adenomas induced by PLAG1 versus normal salivary glands. Concordance between these two sets of experiments pinpointed 12 genes that were significantly and consistently upregulated in pleomorphic adenomas and in PLAG1-expressing cells, identifying them as putative PLAG1 targets in these tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microarray screening for target genes of the proto-oncogene PLAG1

et al. 2004

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“…The findings that even in cntf/lif/ct-1 triple-knock-out mice motor function and motoneuron survival are not completely abolished supports this view. Among these potential additional CNTF-like ligands, neuropoietin (Derouet et al, 2004) and the composite cytokine formed by cardiotrophin-like cytokine (CLC) (Senaldi et al, 1999;Shi et al, 1999) and the soluble receptor cytokine-like factor-1 (CLF) (Alexander et al, 1999;Elson et al, 2000) are likely candidates. Both factors have been identified recently as additional ligands for the CNTF receptor complex (Plun-Favreau et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Holtmann¹,

Wiese²,

Samsam³

et al. 2005

J. Neurosci.

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Members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor (LIF) gene family play an essential role for survival of developing and postnatal motoneurons. When subunits of the shared receptor complex are inactivated by homologous recombination, the mice die at approximately birth and exhibit reduced numbers of motoneurons in the spinal cord and brainstem nuclei. However, mice in which cntf, lif, or cardiotrophin-1 (ct-1) are inactivated can survive and show less motoneuron cell loss. This suggests cooperative and redundant roles of these ligands. However, their cooperative functions are not well understood. We generated cntf/lif/ct-1 triple-knockout and combinations of double-knock-out mice to study the individual and combined roles of CNTF, LIF and CT-1 on postnatal motoneuron survival and function. Triple-knock-out mice exhibit increased motoneuron cell loss in the lumbar spinal cord that correlates with muscle weakness during early postnatal development. LIF deficiency leads to pronounced loss of distal axons and motor endplate alterations, whereas CNTF-and/or CT-1-deficient mice do not show significant changes in morphology of these structures. In cntf/lif/ct-1 triple-knock-out mice, various degrees of muscle fiber type grouping are found, indicating that denervation and reinnervation had occurred. We conclude from these findings that CNTF, LIF, and CT-1 have distinct functions for motoneuron survival and function and that LIF plays a more important role for postnatal maintenance of distal axons and motor endplates than CNTF or CT-1.

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“…The sections were acetylated twice in 0.1 M triethanolamine and acetic anhydride at room temperature for 10 min and washed twice with PBS, followed by dehydration in 30,50, 70, 90, 95, and 100% ethanol for 5 min each. After dipping in chloroform for 5 min at room temperature and in 0.2ϫ SSC for 1-2 min, prehybridization was carried out in a moist chamber with 50% formamide in 5ϫ SSC at 45°C for 3 h. For hybridization, 35 S-UTP-labeled antisense and sense RNAs encoding the Mgat3 gene coding region were prepared from a mouse Mgat3 cDNA (6) using T7 or SP6 RNA polymerase (Promega); probes were hydrolyzed; and hybridization, washing, and autoradiography were performed as described previously (26).…”

Section: Matrix-assisted Laser Desorption/ionization Time-of-flight Mmentioning

confidence: 99%

Truncated, InactiveN-Acetylglucosaminyltransferase III (GlcNAc-TIII) Induces Neurological and Other Traits Absent in Mice That Lack GlcNAc-TIII

Bhattacharyya

Bhaumik

Raju³

et al. 2002

Journal of Biological Chemistry

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N-Acetylglucosaminyltransferase III (GlcNAc-TIII), the product of the Mgat3 gene, transfers the bisecting GlcNAc to the core mannose of complex N-glycans. The addition of this residue is regulated during development and has functional consequences for receptor signaling, cell adhesion, and tumor progression. Mice homozygous for a null mutation at the Mgat3 locus (Mgat3 ⌬ ) or for a targeted mutation in the Mgat3 gene (previously called Mgat3 neo , but herein renamed Mgat3 T37 because the allele generates inactive GlcNAc-TIII of ϳ37 kDa) were found to exhibit retarded progression of liver tumors. Matrix-assisted laser desorption/ionization time-offlight mass spectrometry of neutral N-glycans from kidneys revealed no significant differences, and both mutants showed the expected lack of N-glycan species with an additional GlcNAc. However, the two mutants differed in several biological traits. Mgat3 T37/T37 homozygotes in a mixed or 129SvJ background were retarded in growth rate and exhibited an altered leg clasp reflex, an altered gait, and defective nursing behavior. Pups abandoned by Mgat3 T37/T37 mothers were rescued by wildtype foster mothers. None of these Mgat3 T37/T37 traits were exhibited by Mgat3 ⌬/⌬ mice or by heterozygous mice carrying the Mgat3 T37 mutation. Similarly, no dominant-negative effect was observed in Chinese hamster ovary cells expressing truncated GlcNAc-TIII in the presence of wild-type GlcNAc-TIII. However, compound heterozygotes carrying both the Mgat3 T37 and Mgat3 ⌬ mutations exhibited a marked leg clasp reflex, indicating that in the absence of wild-type GlcNAc-TIII, truncated GlcNAc-TIII causes this phenotype. The Mgat3 gene was expressed in brain at embryonic day 10.5 and thereafter and in neurons of adult cerebellum. The mutant Mgat3 gene was also highly expressed in Mgat3 T37/T37 brain. This may be the basis of the unexpected neurological phenotype induced by truncated, inactive GlcNAc-TIII in the mouse.The N-glycans of mammalian glycoproteins vary widely in structure, but the biological significance of this variation is largely unknown. A well studied example is the bisecting GlcNAc. This residue is transferred to the ␤-linked Man of the core of N-glycans by the glycosyltransferase termed N-acetylglucosaminyltransferase III (GlcNAc-TIII 1 ; EC 2.4.1.144) (1), the product of the Mgat3 gene (2). The presence of the bisecting GlcNAc alters the lectin binding properties of a cell, a fact initially revealed by the gain-of-function Chinese hamster ovary (CHO) glycosylation mutant LEC10, which expresses GlcNAc-TIII (3). LEC10 cells are ϳ15-fold more resistant to ricin and ϳ10-fold more sensitive to the toxicity of the erythroagglutinin from Phaseolus vulgaris (E-PHA) compared with wild-type CHO cells, reflecting dramatic changes in binding of these lectins to N-linked Gal residues of cell-surface glycoproteins. Similarly, the ectopic expression of an Mgat3 cDNA reduces the expression of terminal ␣3-Gal residues, a key determinant in xenotransplantation (4, 5). The regulated expression o...

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Suckling defect in mice lacking the soluble haemopoietin receptor NR6

Cited by 71 publications

References 10 publications

Microarray screening for target genes of the proto-oncogene PLAG1

Microarray screening for target genes of the proto-oncogene PLAG1

Triple Knock-Out ofCNTF,LIF, andCT-1Defines Cooperative and Distinct Roles of these Neurotrophic Factors for Motoneuron Maintenance and Function

Truncated, InactiveN-Acetylglucosaminyltransferase III (GlcNAc-TIII) Induces Neurological and Other Traits Absent in Mice That Lack GlcNAc-TIII

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