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Many ribosomal protein mutations are associated with growth impairment and tumor predisposition in zebrafish
Author(s) -
Lai Kevin,
Amsterdam Adam,
Farrington Sarah,
Bronson Roderick T.,
Hopkins Nancy,
Lees Jacqueline A.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21815
Subject(s) - biology , zebrafish , loss of heterozygosity , carcinogenesis , heterozygote advantage , gene , compound heterozygosity , cancer research , genetics , mutation , translation (biology) , ribosomal protein , microbiology and biotechnology , messenger rna , ribosome , rna , allele
We have characterized 28 zebrafish lines with heterozygous mutations in ribosomal protein ( rp ) genes, and found that 17 of these are prone to develop zebrafish malignant peripheral nerve sheath tumors (zMPNST). Heterozygotes from the vast majority of tumor‐prone rp lines were found to be growth‐impaired, though not all growth‐impaired rp lines were tumor‐prone. Significantly, however, the rp lines with the greatest incidence of zMPNSTs all displayed a growth impairment. Furthermore, heterozygous cells from one tumor‐prone rp line were out‐competed by wild‐type cells in chimeric embryos. The growth impairment resulting from heterozygosity for many rp genes suggests that a global defect in protein translation exists in these lines, raising the possibility that a translation defect that precedes tumor development is predictive of tumorigenesis. Developmental Dynamics 238:76–85, 2009. © 2008 Wiley‐Liss, Inc.