Table 2.

Current mouse models to study the function of Ift-A proteins in bone development

Gene	Mouse models	Mutation	Cilia	Phenotype	Pathways	Ref
Ift139	Ift139alien	ENU mutagenesis, complete loss-of-function	Short and bulb-like structure cilia with accumulation of complex B proteins in the cilia tip	Defects in limbs, eyes, skull and brain development.	Overactivated Shh pathway Ift139 is the negative regulator in the Shh pathway downstream of Smo and upstream of Gli2, no significant change in Wnt pathway.	(95, 96)
Ift122	Ift122- null	Exon 1–3 mutation of MED1, null mutation	Cilia loss in the homozygous and malformed cilia in heterozygous	Usually die between E10.5 to E13.5. Exencephaly, delay in limb development, defects of the ventral portion of the head, rostral neural tube, eye and branchial arches.	Impaired Shh due to reduced Gli2/Gli3 and Gli3 repressor functions.	(97)
	Ift122sopb	ENU- mutagenesis, complete loss-of-function	Short and swollen cilia with complex B proteins accumulation	Die around E13.5. Neural defects, pre-axial polydactyly, enlarged bronchial arches, and ocular defects.	Enhanced Shh with Gli2 and Gli3 accumulation in the cilia tips but absent of TULP3 in cilia.	(158)
Ift144	Ift144twt	ENU- mutagenesis, partial loss-of-function	Relatively normal cilia structure but reduced frequency	Die at E11.0. Polydactyly, small rib cages, cleft palate and severe craniofacial anomalies.	Ift144twt MEFs respond weakly to stimulation with upstream Hh agonists, a general increase or ectopic activation of Hh in Ift144twt embryos, particularly in the facial prominences and limbs.	(160)
	Ift144dmhd	ENU- mutagenesis complete loss-of-function	Short and had highly disrupted axoneme	Die after E13.0. Polydactyly and craniofacial abnormalities. Smaller forelimb paddle, with truncation in the PD and to a lesser extent the AP axes.	Less activation of the Shh pathway in the caudal neural tube.	(160, 161)
	Ift144twtIft122sopb	Double mutation	Similar to Ift144dmhd	Similar to Ift144dmhd.	Less Shh pathway activity.	(161)
	Ift144twtDync2h1mmi	Double mutation	Reduced cilia number, cilia swollen in Dync2h1mmi	Partially rescued most ventral neural cell type, and the floor plate.	Partial rescue of Shh signaling.	(161)
WDR35 (Ift121)	WDR35yet	ENU- mutagenesis, complete loss-of-function	Cilia loss with Ift88 accumulated in the basal body	Usually die at E12.5. Severe defects in cardiovascular, embryo turning, and limb outgrowth and patterning. Failure of the somite derivatives.	Not reported	(34)
	WDRtm2a	“targeted trap” null allele	Not reported	Phenocopies WDR35yet.	Not reported	(34)
Ift140	Ift140null	Germline deletion with C57Bl/6 Prm-Cre	Not reported	Die at mid-gestation.	Not reported	(162)
	Ift140cauli	ENU- mutagenesis, “possibly damaging” mutation	Cilia morphology was severely disrupted with broader and bulbous appearance	Start to die at E13.5. Exencephaly, anophthalmia, severely disorganised ribs with extensive exostoses, vertebral and palatal defects, agenesis/hypoplasia of the craniofacial skeleton, and polydactyly of the hindlimbs.	Ectopic Hh signaling activation and reduced Gli3 repressor production.	(163, 164)
	Ift140−/−	Germline deletion with CMV-Cre	Not reported	Similar to Ift140cauli.	Not reported	(164)