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Derivation of a mouse model for conditional inactivation of Pax9

Ralf Kist1, Elizabeth Greally, Heiko Peters

  • 1Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.

Genesis (New York, N.Y. : 2000)
|July 5, 2007
PubMed

Insights

Paired box 9 (Pax9) is crucial for organ development. A new conditional Pax9 allele allows researchers to study its postnatal functions, revealing its role in neural crest development for palate and tooth formation.

Area of Science:

  • Developmental biology
  • Genetics
  • Molecular biology

Background:

  • Paired box 9 (Pax9) is essential for embryonic organogenesis in mice.
  • The function of Pax9 in postnatal development is largely unknown due to early lethality associated with null alleles.

Purpose of the Study:

  • To generate and characterize a conditional Pax9 allele for studying its postnatal functions.
  • To investigate the role of Pax9 in neural crest-derived tissues during mouse development.

Main Methods:

  • Generation of a hypomorphic Pax9 allele (Pax9(neo)) with a removable neomycin cassette and loxP sites.
  • In vivo recombination using FLP and Cre-lox systems to generate conditional Pax9 knockout models (Pax9(flox) and Pax9(del/del)).
  • Analysis of developmental defects in Pax9-deficient offspring using Wnt1-Cre and PGK-Cre mice.

Main Results:

  • Conditional Pax9 alleles (Pax9(flox)) were successfully generated and shown to be viable.
  • Inactivation of Pax9 in specific tissues using Wnt1-Cre resulted in neonatal lethality and developmental abnormalities, including cleft secondary palate and tooth agenesis.
  • Pax9-expressing mesenchymal cells in the nose, palate, and teeth were identified as originating from neural crest cells.

Conclusions:

  • The conditional Pax9 allele is a valuable tool for studying Pax9 function in specific tissues of adult mice.
  • Pax9 plays a critical role in the development of neural crest-derived craniofacial structures, including the palate and teeth.

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