RGD Reference Report - Modulation of Erbb2 signaling during development: a threshold level of Erbb2 signaling is required for development. - Rat Genome Database

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Modulation of Erbb2 signaling during development: a threshold level of Erbb2 signaling is required for development.

Authors: Chan, R  Hardy, WR  Dankort, D  Laing, MA  Muller, WJ 
Citation: Chan R, etal., Development 2004 Nov;131(22):5551-60. Epub 2004 Oct 20.
RGD ID: 1358539
Pubmed: PMID:15496447   (View Abstract at PubMed)
DOI: DOI:10.1242/dev.01425   (Journal Full-text)

We have generated a series of Erbb2 cDNA knock-in animals to explore the role of signaling pathways coupled to Erbb2 during development. Although this knock-in allele was hypomorphic, expressing tenfold less Erbb2 protein than wild type, the knock-in animals were healthy. However, a further twofold reduction in Erbb2 levels in hemizygous knock-in animals resulted in perinatal lethality with defects in the innervation of the diaphragm. Genetic rescue of this hypomorph was accomplished by expression of the Erbb2-Y1028F mutant in a comparable knock-in allele. Interestingly, hemizygous Y1028F animals were viable with normal innervation of the diaphragm. Molecular analyses revealed that the Y1028F allele expressed higher levels of Erbb2 and that Y1028 promoted the turnover of the receptor. In addition, ablation of the Shc-binding site in Erbb2 (Y1227) resulted in subtle defects in the sensory nerves not observed in the other mutant erbb2 strains. Thus, we have established how Erbb2 levels may be modulated through development and that a minimum threshold level of Erbb2 is required.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
peripheral nervous system development  IMP 1358539 RGD 
sympathetic nervous system development  IMP 1358539 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)


Additional Information