Hyperactivation of Alk induces neonatal lethality in knock-in AlkF1178L mice
| Autor: | Jean-Loup Duband, Marie-France Champy, Marie-Christine Birling, Hamid Meziane, Evelyne Bloch-Gallego, Isabelle Janoueix-Lerosey, Thomas Bourgeois, Olivier Delattre, Jorge Gallego, Michel Huerre, Tania Sorg, Michel Roux, Boris Matrot, Lucille Lopez-Delisle, Estelle Durand, Cécile Pierre-Eugène |
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| Přispěvatelé: | Bos, Mireille, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), PhenoPups : Preclinical Pediatric Contract Research Organization [Evry], Phenopups SAS [Evry], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pathologie, Institut Curie [Paris], The U830 Inserm laboratory is supported bygrants from the Institut National du Cancer, the LigueNationale contre le Cancer (Equipe labellisée), theAssociation Hubert Gouin, Les Bagouz à Manon, les amisde Claire, la Fédération Enfants et Santé et la SociétéFrançaise de Lutte contre les Cancers et les Leucémiesde l’Enfant et l’Adolescent. L. L.-D. is the recipient ofa fellowship of the Ecole Polytechnique. The InstitutClinique de la Souris was funded by Inserm., Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Clinique de la Souris ( ICS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement ( LBD ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Neuroprotection du Cerveau en Développement ( PROTECT ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), INSTITUT CURIE |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Congenital neuroblastoma MESH : Behavior Animal MESH: Eating Germline MESH: Animals Newborn Feeding difficulty brainstem Immunoenzyme Techniques Eating Mice Neuroblastoma 0302 clinical medicine neonatal lethality hemic and lymphatic diseases MESH: Behavior Animal Anaplastic lymphoma kinase Anaplastic Lymphoma Kinase MESH: Animals feeding difficulties 0303 health sciences Behavior Animal plethysmography MESH : Animals Newborn Respiration 3. Good health MESH : Phenotype Phenotype Oncology 030220 oncology & carcinogenesis Neonatal lethality MESH: Receptor Protein-Tyrosine Kinases MESH : Mutation Research Paper medicine.medical_specialty MESH : Eating MESH: Mutation MESH : Male Biology MESH: Phenotype 03 medical and health sciences Germline mutation MESH : Immunoenzyme Techniques Internal medicine Gene knockin MESH : Mice medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans In patient [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Immunoenzyme Techniques [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice 030304 developmental biology Gynecology MESH: Respiration MESH: Humans MESH : Humans Receptor Protein-Tyrosine Kinases MESH : Receptor Protein-Tyrosine Kinases MESH: Neuroblastoma MESH: Male MESH : Respiration Endocrinology Animals Newborn ALK MESH : Genes Lethal Mutation MESH : Neuroblastoma Genes Lethal MESH : Animals MESH: Genes Lethal |
| Zdroj: | Oncotarget Oncotarget, 2014, 5 (9), pp.2703-13. ⟨10.18632/oncotarget.1882⟩ Oncotarget, Impact journals, 2014, 5 (9), pp.2703-13. ⟨10.18632/oncotarget.1882⟩ Oncotarget, Impact journals, 2014, 5 (9), pp.2703-13. 〈10.18632/oncotarget.1882〉 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.1882⟩ |
| Popis: | // Lucille Lopez-Delisle 1,2 , Cecile Pierre-Eugene 1,2 , Evelyne Bloch-Gallego 3,4 , Marie-Christine Birling 5 , Jean-Loup Duband 6,7 , Estelle Durand 8 , Thomas Bourgeois 8 , Boris Matrot 8,9 , Tania Sorg 5 , Michel Huerre 10 , Hamid Meziane 5 , Michel J. Roux 5 , Marie-France Champy 5 , Jorge Gallego 9 , Olivier Delattre 1,2 , Isabelle Janoueix-Lerosey 1,2 1 Inserm U830, Paris, France; 2 Institut Curie, Centre de Recherche, Paris, France; 3 Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France; 4 Inserm, U1016, Paris, France; 5 Institut Clinique de la Souris, Illkirch-Graffenstaden, France; 6 Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; 7 CNRS, Laboratoire de Biologie du Developpement, Paris, France; 8 PhenoPups SAS, Evry, France; 9 Inserm U1141, Hopital Robert Debre, Paris, France; 10 Institut Curie, Departement de Pathologie, Paris, France. Correspondence: Isabelle Janoueix-Lerosey, email: // Keywords : ALK, brainstem, neonatal lethality, plethysmography, feeding difficulties Received : March 24, 2014 Accepted : April 01, 2014 Published : April 02, 2014 Abstract The ALK (Anaplastic Lymphoma Kinase) gene encodes a tyrosine kinase receptor preferentially expressed in the central and peripheral nervous systems. A syndromic presentation associating congenital neuroblastoma with severe encephalopathy and an abnormal shape of the brainstem has been described in patients harbouring de novo germline F1174V and F1245V ALK mutations. Here, we investigated the phenotype of knock-in (KI) mice bearing the Alk F1178L mutation (F1174L in human). Although heterozygous KI mice did not reproduce the severe breathing and feeding difficulties observed in human patients, behavioral tests documented a reduced activity during dark phases and an increased anxiety of mutated mice. Matings of heterozygotes yielded the expected proportions of wild-type, heterozygotes and homozygotes at birth but a high neonatal lethality was noticed for homozygotes. We documented Alk expression in several motor nuclei of the brainstem involved in the control of sucking and swallowing. Evaluation of basic physiological functions 12 hours after birth revealed slightly more apneas but a dramatic reduced milk intake for homozygotes compared to control littermates. Overall, our data demonstrate that Alk activation above a critical threshold is not compatible with survival in mice, in agreement with the extremely severe phenotype of patients carrying aggressive de novo ALK germline mutations. |
| Databáze: | OpenAIRE |
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