PMID- 10611327
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 26
DP  - 1999 Dec 21
TI  - Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene
      lhx8.
PG  - 15002-6
AB  - Formation of the mammalian secondary palate is a highly regulated and complex
      process whose impairment often results in cleft palate, a common birth defect in 
      both humans and animals. Loss-of-function analysis has linked a growing number of
      genes to this process. Here we report that Lhx8, a recently identified LIM
      homeobox gene, is expressed in the mesenchyme of the mouse palatal structures
      throughout their development. To test the function of Lhx8 in vivo, we generated 
      a mutant mouse with a targeted deletion of the Lhx8 gene. Our analysis of the
      mutant animals revealed a crucial role for Lhx8 in palatogenesis. In Lhx8
      homozygous mutant embryos, the bilateral primordial palatal shelves formed and
      elevated normally, but they often failed to make contact and to fuse properly,
      resulting in a cleft secondary palate. Because development of other craniofacial 
      structures appeared normal, the impaired palatal formation in Lhx8-mutant mice
      was most likely caused by an intrinsic primary defect in the mesenchyme of the
      palatal shelves. The cleft palate phenotype observed in Lhx8-mutant mice suggests
      that Lhx8 is a candidate gene for the isolated nonsyndromic form of cleft palate 
      in humans.
FAU - Zhao, Y
AU  - Zhao Y
AD  - Laboratory of Mammalian Genes and Development, National Institute of Child Health
      and Human Development, Bethesda, MD 20892, USA.
FAU - Guo, Y J
AU  - Guo YJ
FAU - Tomac, A C
AU  - Tomac AC
FAU - Taylor, N R
AU  - Taylor NR
FAU - Grinberg, A
AU  - Grinberg A
FAU - Lee, E J
AU  - Lee EJ
FAU - Huang, S
AU  - Huang S
FAU - Westphal, H
AU  - Westphal H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Homeodomain Proteins)
RN  - 0 (LIM homeobox protein 8)
RN  - 0 (LIM-Homeodomain Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Cleft Palate/*genetics
MH  - Gene Expression
MH  - *Genes, Homeobox
MH  - Homeodomain Proteins/*genetics
MH  - In Situ Hybridization
MH  - LIM-Homeodomain Proteins
MH  - Mice
MH  - Mice, Knockout
MH  - Palate/*embryology/pathology
MH  - Protein Structure, Tertiary
MH  - RNA, Messenger/isolation & purification
MH  - Tissue Distribution
MH  - Transcription Factors/*genetics
PMC - PMC24762
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1073/pnas.96.26.15002 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15002-6. doi:
      10.1073/pnas.96.26.15002.