RGD Reference Report - A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia. - Rat Genome Database

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A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia.

Authors: Flenniken, AM  Osborne, LR  Anderson, N  Ciliberti, N  Fleming, C  Gittens, JE  Gong, XQ  Kelsey, LB  Lounsbury, C  Moreno, L  Nieman, BJ  Peterson, K  Qu, D  Roscoe, W  Shao, Q  Tong, D  Veitch, GI  Voronina, I  Vukobradovic, I  Wood, GA  Zhu, Y  Zirngibl, RA  Aubin, JE  Bai, D  Bruneau, BG  Grynpas, M  Henderson, JE  Henkelman, RM  McKerlie, C  Sled, JG  Stanford, WL  Laird, DW  Kidder, GM  Adamson, SL  Rossant, J 
Citation: Flenniken AM, etal., Development. 2005 Oct;132(19):4375-86.
RGD ID: 8662372
Pubmed: PMID:16155213   (View Abstract at PubMed)
DOI: DOI:10.1242/dev.02011   (Journal Full-text)

Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder characterized by pleiotropic developmental anomalies of the limbs, teeth, face and eyes that was shown recently to be caused by mutations in the gap junction protein alpha 1 gene (GJA1), encoding connexin 43 (Cx43). In the course of performing an N-ethyl-N-nitrosourea mutagenesis screen, we identified a dominant mouse mutation that exhibits many classic symptoms of ODDD, including syndactyly, enamel hypoplasia, craniofacial anomalies and cardiac dysfunction. Positional cloning revealed that these mice carry a point mutation in Gja1 leading to the substitution of a highly conserved amino acid (G60S) in Cx43. In vivo and in vitro studies revealed that the mutant Cx43 protein acts in a dominant-negative fashion to disrupt gap junction assembly and function. In addition to the classic features of ODDD, these mutant mice also showed decreased bone mass and mechanical strength, as well as altered hematopoietic stem cell and progenitor populations. Thus, these mice represent an experimental model with which to explore the clinical manifestations of ODDD and to evaluate potential intervention strategies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
oculodentodigital dysplasia  ISOGja1 (Mus musculus)8662372; 8662372DNA:missense mutation:cds:p.G60S (mouse)RGD 
oculodentodigital dysplasia  IAGP 8662372DNA:missense mutation:cds:p.G60S (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gja1  (gap junction protein, alpha 1)

Genes (Mus musculus)
Gja1  (gap junction protein, alpha 1)

Genes (Homo sapiens)
GJA1  (gap junction protein alpha 1)


Additional Information