Nestin-Cre mediated deletion of Pitx2 in the mouse.
Nestin-Cre mice are widely used to generate gene deletions in the developing brain. Surprisingly, fewNestin-Cre lines have been characterized for their temporal and brain region-specific recombination. In addition, some Nestin-Cre lines express Cre outside the central nervous system, making it difficult to choose appropriate lines for targeting genes with brain region-restricted expression. Here we describe the properties of a Nestin-Cre transgenic line and its use for conditional deletions of Pitx2, a paired-like homeodomain transcription factor. We report that Nestin-Cre conditional Pitx2 mutant mice have ocular and craniofacial defects consistent with the role of human PITX2 in Rieger syndrome. Conditional mutants exhibit defects in midbrain neuronal development similar to those in Pitx2 homozygous null embryos, but lack the abnormalities in subthalamic nucleus neurons that occur with complete loss of Pitx2 function. These data indicate that normal differentiation of midbrain neurons depends upon adequate Pitx2 function during the period of active neurogenesis.
Sclafani
Anthony M
AM
Molecular, Cellular and Developmental Biology Graduate Program, Yale College of Medicine, New Haven, Connecticut, USA.
Skidmore
Jennifer M
JM
Ramaprakash
Hemanth
H
Trumpp
Andreas
A
Gage
Philip J
PJ
Martin
Donna M
DM
D000818:Animals; D001921:Brain / Q000196:embryology; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics*; D019426:Integrases / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D009687:Nuclear Proteins / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D019426:Integrases; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D009687:Nuclear Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C577484:NES protein, human; C577485:Nes protein, mouse; C045073:Cre recombinase