Table 2.

Mutations in genes related to cilia and their phenotypes in several cellular and animal models.

Human gene	Model	Mutation	Pancreatic phenotype	Cell line phenotype	References
BBS1	Zebrafish	Bbs1-deficient	Increased β-cells mass and decreased α- and δ-cells cell types in early developmental stages	N/A	(157)
BBS4	Mouse Zebrafish Min6 cells	Bbs4-/- Downregulation of Bbs4	Mice: Islets size was not affected despite impaired glucose homeostasis and obesity onset. Insulin levels reported are either normal or increased Zebrafish: Increased β-cells mass and decreased α- and δ-cells cell types in early developmental stages	Loss of first phase insulin release. Unstimulated Min6 lacked both insulin receptor isoforms (IR-A or IR-B) in the cilium, after insulin stimulation IR-A, but not IR-B, was recruited to the cilium	(143, 157, 158)
BBS5, BBS7, BBS9	Min6 cells	Downregulation of Bbs5, Bbs7, and Bbs9	N/A	~2-fold increase in insulin secretion	(159)
BBS12	Mouse	Bbs12-/-	Islets size and plasma insulin levels were not affected despite enhanced in vivo insulin sensitivity	N/A	(160)
AMLS1	Mouse Zebrafish β-TC-6 cells	Amls1-/- Downregulation of Amls1	Mice: Pancreatic hyperplasia, partial degranulation of β-cells and islets cysts Zebrafish: Decreased β-cells production, hyperinsulinemia and impaired glucose-stimulated insulin secretion	Modest hypersecretory basal state in unstimulated cells, impaired glucose-stimulated insulin secretion and altered gene expression for signals downstream of glucose transport	(157, 161–163)
AMLS1	Mouse	Alms1L2131X/L2131X	Stunted cilia and loss of calcium signaling	N/A	(164)
IFT88	Mouse	Ift88/Polaris-/-	Loss of cilia in ductal and endocrine cells, cystogenesis, abnormal tubular structures, endocrine cells in duct, acinar cells apoptosis, endocrine islets normal except for increased β-cells clustering	N/A	(10, 130)
KIF3A	Mouse Min6 cells	Kif3a-/- Downregulation of Kif3a	Loss of cilia in ductal and endocrine cells, leading to acinar-to-ductal metaplasia, fibrosis, cyst formation, aberrant ductal cell morphology and lipomatosis	Decreased proliferation	(10, 165)
HNF6	Mouse	Hnf6-/-	Loss of ductal primary cilium, enlarged lumen and multiple cysts. Delayed Pdx1 expression and hypoplastic pancreas with retarded pancreatic specification of endodermal cells	N/A	(166–168)
RFX3	Mouse	Rfx3-/-	Reduced and stunned primary cilia. Reduced β-cells, α-cells, and δ-cells, increased pancreatic polypeptide-positive cells in perinatal stages. Adults showed small and disorganized islets, decreased insulin production, reduced glucose-stimulated insulin section, and impaired glucose tolerance	N/A	(155)
LKB1/STK11	Mouse	Lkb1-/-	Reduced β-cells, α-cells, and δ-cells number. Altered localization of cilia in β-cells and increased β-cells volume and insulin secretion in vivo with improved glucose tolerance	N/A	(169–172)
IDE	Mouse INS1E cells Mouse	Ide-/- in β-cells Downregulation of Ide Ide-/- in α-cells	B-IDE-KO: Impaired glucose-simulated insulin secretion. β-cell immaturity with constitutive insulin and pro-insulin secretion, decreased gene expression of Ins2, Ucn3, and Pcsk1, decreased GLUT2 plasma membrane levels A-IDE-KO: Impaired ciliogenesis, α-cells hyperplasia, and hypertrophy, impaired insulin inhibition of glucagon secretion, hyperglucagonemia and hyperinsulinemia, but normal glucose tolerance	Impaired GSIS N/A	(173, 174) (175)