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Perinatal lethality and multiple craniofacial malformations in MSX2 transgenic mice
J Winograd1, M P Reilly, R Roe
1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore MD 21287, USA.
Human Molecular Genetics
|March 1, 1997
Summary
The homeobox gene MSX2 is crucial for craniofacial development. Mouse models show that MSX2 mutations cause severe craniofacial malformations by affecting neural crest cell survival.
Area of Science:
- Developmental Biology
- Genetics
- Craniofacial Biology
Background:
- MSX2 is a homeodomain transcription factor involved in craniofacial development.
- A specific MSX2 mutation (P148H) is linked to Boston-type craniosynostosis in humans.
Purpose of the Study:
- To investigate the role of MSX2 in craniofacial morphogenesis using transgenic mouse models.
- To determine the effects of wild-type and mutant MSX2 on craniofacial development and cell survival.
Main Methods:
- Generation of transgenic mice carrying human wild-type or mutant (P148H) MSX2 genes.
- Analysis of craniofacial phenotypes, including skeletal malformations and tissue development.
- Assessment of the impact on neural crest-derived cells.
Main Results:
- Transgenic mice exhibited perinatal lethality and severe craniofacial malformations (e.g., mandibular hypoplasia, cleft palate, exencephaly).
- Observed malformations included interparietal bone aplasia and reduced hyoid ossification.
- Malformations affected cranial neural-crest derivatives, showing tissue deficiency and resembling effects of teratogens like ethanol and retinoic acid.
Conclusions:
- MSX2 plays a critical role in regulating the balance between survival and apoptosis of neural crest-derived cells.
- Aberrant MSX2 activity, whether wild-type or mutant, disrupts craniofacial development by impacting cell death pathways.
- These findings highlight MSX2's importance in ensuring proper craniofacial morphogenesis.