Generation of mice with functional inactivation oftalpid3, a gene first identified in chicken

• DOI: 10.1242/dev.063602
• Publication Date: 2011-07-12T11:32:44Z
• Authors: Fiona Bangs; Nicole Antonio; Peerapat Thongnuek; Monique Welten; Megan G. Davey; James Briscoe; Cheryll Tickle
• Keywords: Mesenchyme; Lateral plate mesoderm; GLI3; Ciliogenesis

Specification of digit number and identity is central to pattern in vertebrate limbs. The classical talpid(3) chicken mutant has many unpatterned digits together with defects other regions, depending on hedgehog (Hh) signalling, exhibits embryonic lethality. a mutation KIAA0586, which encodes centrosomal protein required for the formation primary cilia, are sites Hh signalling. highly conserved exons 11 12 KIAA0586 essential rescue cilia mutants. We constitutively deleted these two make talpid3(-/-) mouse. Mutant mouse embryos lack and, like embryos, have face neural tube but also left/right asymmetry. Conditional deletion limb mesenchyme results polydactyly brachydactyly failure subperisoteal bone formation, that attributable abnormal sonic Indian respectively. Like limbs, limbs syndactylous uneven spacing as reflected altered Raldh2 expression, normally associated interdigital mesenchyme. Both buds broad short. cells migrate more slowly than wild-type cells, change cell behaviour possibly contributes bud morphogenesis. This genetic model will facilitate further conditional approaches, epistatic experiments open up investigation into function novel talpid3 gene using resources available mice.