Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice

Vassiliki Fotaki, Mara Dierssen, Soledad Alcántara, Salvador Martínez, Eulàlia Martí, Caty Casas, Joana Visa, Eduardo Soriano, Xavier P. Estivill, Maria L. Arbonés

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in DyrklA function by gene targeting. Dyrk1A-/- null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/-) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/- mice and specific alterations in adults. Brains of Dyrk1A+/- mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.

Original languageEnglish
Pages (from-to)6636-6647
Number of pages12
JournalMolecular and Cellular Biology
Volume22
Issue number18
DOIs
Publication statusPublished - Sep 2002
Externally publishedYes

Fingerprint

Haploinsufficiency
Brain
Diptera
Chromosomes, Human, Pair 21
Gene Targeting
Superior Colliculi
Neurogenesis
Body Size
Growth
Down Syndrome
Genes
Drosophila
Cell Count
Parturition
Neurons
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Fotaki, V., Dierssen, M., Alcántara, S., Martínez, S., Martí, E., Casas, C., ... Arbonés, M. L. (2002). Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Molecular and Cellular Biology, 22(18), 6636-6647. https://doi.org/10.1128/MCB.22.18.6636-6647.2002

Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. / Fotaki, Vassiliki; Dierssen, Mara; Alcántara, Soledad; Martínez, Salvador; Martí, Eulàlia; Casas, Caty; Visa, Joana; Soriano, Eduardo; Estivill, Xavier P.; Arbonés, Maria L.

In: Molecular and Cellular Biology, Vol. 22, No. 18, 09.2002, p. 6636-6647.

Research output: Contribution to journalArticle

Fotaki, V, Dierssen, M, Alcántara, S, Martínez, S, Martí, E, Casas, C, Visa, J, Soriano, E, Estivill, XP & Arbonés, ML 2002, 'Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice', Molecular and Cellular Biology, vol. 22, no. 18, pp. 6636-6647. https://doi.org/10.1128/MCB.22.18.6636-6647.2002
Fotaki, Vassiliki ; Dierssen, Mara ; Alcántara, Soledad ; Martínez, Salvador ; Martí, Eulàlia ; Casas, Caty ; Visa, Joana ; Soriano, Eduardo ; Estivill, Xavier P. ; Arbonés, Maria L. / Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. In: Molecular and Cellular Biology. 2002 ; Vol. 22, No. 18. pp. 6636-6647.
@article{700e4c705e414fa7851a300902c4fb2a,
title = "Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice",
abstract = "DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in DyrklA function by gene targeting. Dyrk1A-/- null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/-) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/- mice and specific alterations in adults. Brains of Dyrk1A+/- mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.",
author = "Vassiliki Fotaki and Mara Dierssen and Soledad Alc{\'a}ntara and Salvador Mart{\'i}nez and Eul{\`a}lia Mart{\'i} and Caty Casas and Joana Visa and Eduardo Soriano and Estivill, {Xavier P.} and Arbon{\'e}s, {Maria L.}",
year = "2002",
month = "9",
doi = "10.1128/MCB.22.18.6636-6647.2002",
language = "English",
volume = "22",
pages = "6636--6647",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "18",

}

TY - JOUR

T1 - Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice

AU - Fotaki, Vassiliki

AU - Dierssen, Mara

AU - Alcántara, Soledad

AU - Martínez, Salvador

AU - Martí, Eulàlia

AU - Casas, Caty

AU - Visa, Joana

AU - Soriano, Eduardo

AU - Estivill, Xavier P.

AU - Arbonés, Maria L.

PY - 2002/9

Y1 - 2002/9

N2 - DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in DyrklA function by gene targeting. Dyrk1A-/- null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/-) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/- mice and specific alterations in adults. Brains of Dyrk1A+/- mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.

AB - DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in DyrklA function by gene targeting. Dyrk1A-/- null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/-) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/- mice and specific alterations in adults. Brains of Dyrk1A+/- mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.

UR - http://www.scopus.com/inward/record.url?scp=0036724569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036724569&partnerID=8YFLogxK

U2 - 10.1128/MCB.22.18.6636-6647.2002

DO - 10.1128/MCB.22.18.6636-6647.2002

M3 - Article

VL - 22

SP - 6636

EP - 6647

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 18

ER -