TY - JOUR
T1 - A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein
AU - Wang, Xin
AU - Bornslaeger, Elayne A.
AU - Haub, Olivia
AU - Tomihara-Newberger, Carol
AU - Lonberg, Nils
AU - Dinulos, Mary Beth
AU - Disteche, Christine M.
AU - Copeland, Neal
AU - Gilbert, Debra J.
AU - Jenkins, Nancy A.
AU - Lacy, Elizabeth
N1 - Funding Information:
We thank Rosemary Bachvarova, Katia Manova, and Lee Nis-wander for helpful discussions and for critical reading of the manuscript. We are also grateful for Katia Manova's advice and assistance on the in situ hybridization assay. We thank Jamie Lee and Frank Costantini for the Hβ58 probe, Patrick Morcillo for valuable assistance in our sequence database searches, and Brian Cho and Mary Barnstead for excellent technical assistance. E.A.B. and N.L. were recipients, respectively, of a postdoctoral fellowship from the National Institutes of Health (NIH) and the American Cancer Society; O.H. is currently a recipient of a postdoctoral fellowship from NIH (GM 15773). This research was supported, in part, by grants from the NIH (HD20919 and AI30502) to E.L. and by the National Cancer Institute, DHHS, under Contract NO1-CO-46000 with ABL. We also acknowledge the support of Memorial Sloan-Kettering Cancer Center Support Grant NCI-P30-CA-08748.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1996/7/10
Y1 - 1996/7/10
N2 - We report the identification of a new recessive prenatal lethal insertional mutation, amnionless (amn). amn mutant embryos first appear abnormal during the Early Streak stage, between E6.5 and E7.0, when they initiate mesoderm production. Subsequently, the amn mutants become developmentally arrested between the Mid and Late Streak stages of gastrulation and they die and are resorbed between E9.5 and E10.5. While extraembryonic structures, including the chorion, yolk sac blood islands, and allantois appear to develop normally, the small embryonic ectoderm remains undifferentiated and generates no amnion. In addition, the embryonic mesoderm that is produced does not become organized into node, notochord, and somites and there is no morphological evidence of neural induction. Interspecific backcross and fluorescence in situ hybridization analyses map the transgene insertion, and thus the amn mutation, to the distal region of mouse chromosome 12, which has synteny with human chromosome 14q32. A gene encoding a 7.5-kb transcript has been identified at a junction between the integrated transgene and host chromosome 12 sequences that meets three criteria expected of a candidate amn gene. This gene maps to the site of transgene insertion; it is transcribed during gastrulation, and its expression is disrupted in amn mutant embryos. Nucleotide sequencing studies show that the 567 amino acid protein encoded by the 7.5-kb transcript is a member of the newly defined family of putative signal transducing proteins, TRAFs, that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. Thus, we have named the gene encoding the 7.5-kb transcript TRAFamn. TRAFamn is identical to a recently reported protein (CD40bp, CAP-1, CRAF1, LAP1) that can bind the cytoplasmic domains of CD40 and the lymphotoxin β receptor (LTβR), both of which are known members of the TNF receptor superfamily. The implications of these findings regarding a possible role for the TNF receptor superfamily during gastrulation are discussed.
AB - We report the identification of a new recessive prenatal lethal insertional mutation, amnionless (amn). amn mutant embryos first appear abnormal during the Early Streak stage, between E6.5 and E7.0, when they initiate mesoderm production. Subsequently, the amn mutants become developmentally arrested between the Mid and Late Streak stages of gastrulation and they die and are resorbed between E9.5 and E10.5. While extraembryonic structures, including the chorion, yolk sac blood islands, and allantois appear to develop normally, the small embryonic ectoderm remains undifferentiated and generates no amnion. In addition, the embryonic mesoderm that is produced does not become organized into node, notochord, and somites and there is no morphological evidence of neural induction. Interspecific backcross and fluorescence in situ hybridization analyses map the transgene insertion, and thus the amn mutation, to the distal region of mouse chromosome 12, which has synteny with human chromosome 14q32. A gene encoding a 7.5-kb transcript has been identified at a junction between the integrated transgene and host chromosome 12 sequences that meets three criteria expected of a candidate amn gene. This gene maps to the site of transgene insertion; it is transcribed during gastrulation, and its expression is disrupted in amn mutant embryos. Nucleotide sequencing studies show that the 567 amino acid protein encoded by the 7.5-kb transcript is a member of the newly defined family of putative signal transducing proteins, TRAFs, that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. Thus, we have named the gene encoding the 7.5-kb transcript TRAFamn. TRAFamn is identical to a recently reported protein (CD40bp, CAP-1, CRAF1, LAP1) that can bind the cytoplasmic domains of CD40 and the lymphotoxin β receptor (LTβR), both of which are known members of the TNF receptor superfamily. The implications of these findings regarding a possible role for the TNF receptor superfamily during gastrulation are discussed.
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U2 - 10.1006/dbio.1996.0162
DO - 10.1006/dbio.1996.0162
M3 - Article
C2 - 8660894
AN - SCOPUS:0030578435
VL - 177
SP - 274
EP - 290
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -