Table 4.

Current mouse models to study the function of Ift retrograde motors in bone development

Gene	Mouse models	Mutation	Cilia	Phenotype	Pathways	Ref
Dync2h1	Dnchc2lln	ENU- mutagenesis, missense mutation	Abnormal cilia with reduced length and bulge along their length	Die at approximately E12.5, abnormal brain morphology, randomization of heart-looping polarity and polydactylous.	Defects in Hh pathways with high level of Smo, Gli2 and Ptch1 accumulation along the cilia with or without Shh stimulation.	(48, 204)
	Dnchc2GT	Gene trap insertion, null allele	Not reported	Similar to Dnchc2lln.	Not reported	(48)
	Dync2h1ttn	ENU- mutagenesis, deletion in AAA domain 4	Abnormal cilia with reduced length and bulges along the axoneme	Not reported	Transportation of activated Gli2 out of cilia is blocked. Wnt signaling is normal in midgestation embryo or embryo-derived fibroblasts.	(67, 205)
	Dnchc2Q397Stop	ENU- mutagenesis, null mutation	Shorter and wider cilia	Die at E12.0 or earlier with pericardial edema and heart failure. Severe defects in dorsoventral patterning of the forebrain and patterning of the spinal cord.	Both Gli activator and Gli repressor activity were significantly reduced. Disruption in Gli3 proteolytic processing and Smo localization to cilia.	(207)
	Dnchc2W2502R	ENU- mutagenesis, null mutation	Shorter and wider cilia	Similar to Dnchc2Q397Stop.	Similar to Dnchc2Q397Stop.	(207)
	Dync2h1mmi	ENU- mutagenesis, missense mutation	Swollen and filled with electron-dense particles and defects in axonemal	Defects in neural tube and motor neurons.	Not reported	(161, 206)
	Dync2h1lln Ift172wim	Double mutation	Absent of cilia	Similar to Ift172wim.	Not reported	(204)
	Dync2h1lln Ift172avc1 and Dync2h1lln/llnIft172avc1/+	Double mutation	Normal morphology in Dync2h1lln/llnIft172avc1/+	Dync2h1lln phenotype can be rescued by reducing Ift172 expression, more dramatic rescue of the Dync2h1 phenotype in Dync2h1lln/llnIft172avc1/+ (survived to at least E16.5 with nearly normal neural patterning in the caudal neural tube).	No Ift or Hh pathway proteins accumulate in cilia, and Hh target gene expression appears to be normal.	(204)
	Ift122sopbDync2h1lln	Double mutation	Similar to Ift122sopb	Similar to Ift122sopb.	Ectopic activity of the Shh pathway in the neural tube. Gli2 limited to the tips of cilia and Smo was not in cilia without Shh stimulation.	(204)
	Dync2h1lln/llnIft122sopb/+	Double mutation	Partially rescued the cilia morphology	Partially rescued the phenotype of Dync2h1lln/lln including ventral neural development.	Partially rescued Shh-dependent protein trafficking in cilia.	(204)
mD2LIC	mD2LIC−/−	Gene targeting, null mutation	Cilia fail to form in the node	mD2LIC−/− died before E11.5 with defects in notochord and floorplate formation and a reduction in definitive endoderm.	Reduction in Hh activity.	(210)