Mice lacking the homologue of the human 22q11.2 gene CRLK phenocopy neurocristopathies of DiGeorge syndrome

Deborah L. Guris, Judith Fantes, David Tara, Brian Druker, Akira Imamoto

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Heterozygous deletions within human chromosome 22q11 are the genetic basis of DiGeorge/velocardiofacial syndrome (DGS/VCFS), the most common deletion syndrome (1 in 4,000 live births) in humans. CRKL maps within the common deletion region for DGS/VCFS (ref. 2) and encodes an SH2-SH3-SH3 adapter protein closely related to the Crk gene products. Here we report that mice homozygous for a targeted null mutation at the CrkL locus (gene symbol Crkol for mice) exhibit defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands and craniofacial structures. We show that the migration and early expansion of neural crest cells is unaffected in Crkol-/- embryos. These results therefore indicate an essential stage- and tissue-specific role for Crkol in the function, differentiation, and/or survival of neural crest cells during development. The similarity between the Crkol-/- phenotype and the clinical manifestations of DGS/VCFS implicate defects in CRKL-mediated signaling pathways as part of the molecular mechanism underlying this syndrome.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalNature Genetics
Volume27
Issue number3
DOIs
StatePublished - 2001

Fingerprint

DiGeorge Syndrome
Neural Crest
Genes
Parathyroid Glands
Live Birth
Human Chromosomes
Thoracic Aorta
Ganglia
Thymus Gland
Embryonic Structures
Arteries
Phenotype
Mutation
Survival
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Mice lacking the homologue of the human 22q11.2 gene CRLK phenocopy neurocristopathies of DiGeorge syndrome. / Guris, Deborah L.; Fantes, Judith; Tara, David; Druker, Brian; Imamoto, Akira.

In: Nature Genetics, Vol. 27, No. 3, 2001, p. 293-298.

Research output: Contribution to journalArticle

Guris, Deborah L. ; Fantes, Judith ; Tara, David ; Druker, Brian ; Imamoto, Akira. / Mice lacking the homologue of the human 22q11.2 gene CRLK phenocopy neurocristopathies of DiGeorge syndrome. In: Nature Genetics. 2001 ; Vol. 27, No. 3. pp. 293-298.
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