PMID- 10192400
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20131121
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 4
DP  - 1999 Apr
TI  - Embryonic retinoic acid synthesis is essential for early mouse post-implantation 
      development.
PG  - 444-8
AB  - A number of studies have suggested that the active derivative of vitamin A,
      retinoic acid (RA), may be important for early development of mammalian embryos. 
      Severe vitamin A deprivation in rodents results in maternal infertility,
      precluding a thorough investigation of the role of RA during embryogenesis. Here 
      we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2)
      enzyme is required for mouse embryo survival and early morphogenesis. Raldh2 is
      an NAD-dependent aldehyde dehydrogenase with high substrate specificity for
      retinaldehyde. Its pattern of expression during mouse development has suggested
      that it may be responsible for embryonic RA synthesis. We generated a targeted
      disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die
      at midgestation without undergoing axial rotation (body turning), exhibit
      shortening along the anterioposterior axis and do not form limb buds. Their heart
      consists of a single, medial, dilated cavity. Their frontonasal region is
      truncated and their otocysts are severely reduced. These defects result from a
      block in embryonic RA synthesis, as shown by the lack of activity of
      RA-responsive transgenes, the altered expression of an RA-target homeobox gene
      and the near full rescue of the mutant phenotype by maternal RA administration.
      Our data establish that RA synthesized by the post-implantation mammalian embryo 
      is an essential developmental hormone whose lack leads to early embryo death.
FAU - Niederreither, K
AU  - Niederreither K
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire,
      CNRS/INSERM/ULP/College de France, Illkirch, C.U. de Strasbourg, France.
FAU - Subbarayan, V
AU  - Subbarayan V
FAU - Dolle, P
AU  - Dolle P
FAU - Chambon, P
AU  - Chambon P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fgf3 protein, mouse)
RN  - 0 (Fgf8 protein, mouse)
RN  - 0 (Fibroblast Growth Factor 10)
RN  - 0 (Fibroblast Growth Factor 3)
RN  - 0 (Hand1 protein, mouse)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Otx Transcription Factors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (helix-loop-helix protein, eHAND)
RN  - 0 (homeobox A1 protein)
RN  - 148997-75-5 (Fibroblast Growth Factor 8)
RN  - 5688UTC01R (Tretinoin)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - EC 1.2.- (Aldehyde Oxidoreductases)
RN  - EC 1.2.1.36 (Retinal Dehydrogenase)
SB  - IM
CIN - Nat Genet. 1999 Apr;21(4):346-7. PMID: 10192377
MH  - Abnormalities, Multiple/genetics
MH  - Aldehyde Oxidoreductases/*genetics/*metabolism
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Embryo, Mammalian/abnormalities/metabolism/pathology
MH  - Embryonic Development/*physiology
MH  - Embryonic and Fetal Development/drug effects/*physiology
MH  - Female
MH  - Fibroblast Growth Factor 10
MH  - Fibroblast Growth Factor 3
MH  - Fibroblast Growth Factor 8
MH  - Fibroblast Growth Factors/genetics/metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Homeodomain Proteins/genetics/metabolism
MH  - Limb Buds/abnormalities
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Otx Transcription Factors
MH  - Pregnancy
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Response Elements
MH  - Retinal Dehydrogenase
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transgenes
MH  - Tretinoin/*metabolism/pharmacology
EDAT- 1999/04/07 02:01
MHDA- 2001/03/23 10:01
CRDT- 1999/04/07 02:01
PHST- 1999/04/07 02:01 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/07 02:01 [entrez]
AID - 10.1038/7788 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Apr;21(4):444-8. doi: 10.1038/7788.