PMID- 8555112
OWN - NLM
STAT- MEDLINE
DCOM- 19960227
LR  - 20190909
IS  - 0925-4773 (Print)
IS  - 0925-4773 (Linking)
VI  - 53
IP  - 1
DP  - 1995 Sep
TI  - Mice lacking all isoforms of retinoic acid receptor beta develop normally and are 
      susceptible to the teratogenic effects of retinoic acid.
PG  - 61-71
AB  - Retinoic acids (RA) are vitamin A derivatives essential for normal embryonic 
      development and viability of vertebrates. The RA signal is mediated by two 
      distinct classes of receptors, RA receptors (RARs) and retinoid X receptors 
      (RXRs). The RAR family is composed of three genes: RAR alpha, beta, and gamma. 
      The expression of RAR beta gene is spatially and temporally restricted in certain 
      structures in the developing embryo, suggesting that RAR beta could play specific 
      roles during morphogenesis. Four isoforms of the RAR beta gene (beta 1-beta 4) 
      are generated by differential usage of promoters and alternative splicing. It has 
      recently been demonstrated that the RAR beta 2 isoform is dispensable for normal 
      development. To ascertain the function of all RAR beta isoforms in vivo, we have 
      generated a mutation that disrupts all isoforms of the RAR beta gene in the mouse 
      by gene targeting in embryonic stem cells. Mice homozygous for the mutation are 
      viable and fertile with no externally apparent abnormalities. During development, 
      1/11 RAR beta mutant embryos showed fusion of the ninth and tenth cranial ganglia 
      on both sides of the hindbrain. However, no obvious alterations in the spatial 
      pattern of expression of Hoxb-1, Hoxb-4 and Hoxb-5 were observed in day 9.5 p.c. 
      embryos. The RAR beta null mutation did not alter the pattern or extent of the 
      limb and craniofacial malformations induced by RA excess, suggesting that RAR 
      beta may not be mandatory to mediate the observed teratological effects of RA in 
      these structures. These experiments demonstrate that RAR beta isoforms are not 
      absolutely required for embryonic development and provide additional support to 
      the concept of functional redundancy among members of the RAR family.
FAU - Luo, J
AU  - Luo J
AD  - Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
FAU - Pasceri, P
AU  - Pasceri P
FAU - Conlon, R A
AU  - Conlon RA
FAU - Rossant, J
AU  - Rossant J
FAU - Giguere, V
AU  - Giguere V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Mech Dev
JT  - Mechanisms of development
JID - 9101218
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (retinoic acid receptor beta)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Abnormalities, Drug-Induced/*etiology
MH  - Animals
MH  - Base Sequence
MH  - Embryonic and Fetal Development/*drug effects/genetics
MH  - Extremities/embryology
MH  - Female
MH  - Ganglia/physiology
MH  - *Gene Targeting
MH  - Genes, Homeobox
MH  - Homozygote
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Mutation
MH  - RNA, Messenger/metabolism
MH  - Receptors, Retinoic Acid/genetics/*physiology
MH  - Skull/drug effects/embryology
MH  - Tretinoin/*toxicity
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 0925477395004246 [pii]
AID - 10.1016/0925-4773(95)00424-6 [doi]
PST - ppublish
SO  - Mech Dev. 1995 Sep;53(1):61-71. doi: 10.1016/0925-4773(95)00424-6.