. Author manuscript; available in PMC: 2023 Apr 29.

Published in final edited form as: Biochem Soc Trans. 2022 Apr 29;50(2):689–701. doi: 10.1042/BST20200782

Table 1.

Notch pathway mutant mouse models

Experimental model	Phenotype	Gene expression of Notch target genes		References
Experimental model	Phenotype	Downregulation	Upregulation	References
Villin-CreER^T2; N1^F/F	Increased goblet, enteroendocrine and Paneth cells. Decreased LGR5⁺ and EdU⁺ cells. Loss of Olfm4⁺ cells.	Hes1, Lgr5 and Olfm4	Math1, Ngn3, Spdef, Muc2, ChgA, Mmp7, Dll1 and Dll4	(34)
Villin-CreER^T2; N2^F/F	Unaffected goblet cells	Not reported	No changes in Atoh1, ngn3, Muc2, ChgA, Mmp7, Dll1 and Dll4	(34)
Notch1/Notch2^lox/lox-vil-Cre-ERT2 Villin-CreER^T2; N1^F/F/N2^F/F (N1Δ^/Δ;N2^Δ/Δ)	Highly increased goblet cells. Reduced Hes1⁺ cells.	Hes1	Muc2, Atoh1, Spdef, ChgA, Mmp7, Dll1 and Dll4	(31) (34)
Dll1^flox/flox vil-Cre-ER^T2	Increased goblet cells	Not reported	Not reported	(37)
Dll4^flox/flox vil-Cre-ER^T2	Unaffected goblet cells	Not reported	Not reported	(37)
Dll1-Dll4^vil-Cre-ERT2	Highly increased goblet cells. Decreased Olfm4⁺ cells. Loss of Lgr5⁺, Ascl2⁺, Hes1⁺ Ki67⁺ cells. Inhibited NICD1 cleavage.	Not reported	Math1	(37)
Villin-Cre;Adam10^f/f Villin-CreERT2;Adam10^f/f or organoids from different ADAM10 mutants	Increased goblet, Paneth, enteroendocrine and cleaved caspase-3⁺ cells. Decreased enterocytes, BrdU⁺ and Ki67⁺ cells.	Hes1, HeyL and Olfm4	Tff3, Muc2, Cryptdins, Mmp7, ChgA, Atoh1, Gfi1, Spdef, Ngn3 and Sox9	(20)
γ-secretase inhibitors DBZ/DAPT treatment to mice models or mouse intestinal organoid	Inhibited NICD1 expression. Increased goblet, Paneth enteroendocrine, Tuft, SOX9⁺ and MATH1⁺ cells. Decreased Ki67⁺ and HES1⁺ cells.	Olfm4 and Ascl2	Math1, Lysozyme, Mmp7, EphB3, Ngn3, Spdef, Gfi1, Tff3 and Prom1.	(7, 31–33, 64, 65, 78)
RBP-J^{floxed/floxed}/P450-Cre Rbpj^lox/lox-vil-Cre-ERT2 RBP-J^vil-Cre-ERT2 Rbpj^fl/fl:villin-cre^ER Rbpj^F/F:Villin-CreER^T2	Increased goblet cells and MATH1⁺ cells. Reduced HES1⁺ cells. Loss of Lgr5⁺, Olfm4⁺, Acl2⁺, Hes6⁺ and Ki67⁺ cells.	Hes1	Math1	(32) (31) (37) (64) (34)
Vil-Cre;Rosa26^DN-MAML/+	Increased goblet, Paneth and enteroendocrine cells. Decreased HES1⁺ and Ki67⁺ cells.	Not reported	Not reported	(20)
Embryonic Hes1 KO Hes1-KO pups Villin-Cre;Hes1^flox/– Hes1^fl/fl Cre-ERT2 Hes1^fl/flVillin-Cre	Increased goblet, Paneth, cryptdin 4⁺ and cleaved caspase-3⁺ cells. Decreases Ki67⁺ cells.	Reg3g, Saa1 and Reg3b	Math1, Lysozyme, Cryptdin 1, 4 and 5 Gast, Gcg, Smst, Cck, Sct, Tph, Gip, ChgA, Atoh1, Isl1, Nkx2–2, Pax6, Pax4, Dll1, Dll3, Hes3, Hes5, Tbp, Atoh5 and Neurod1.	(66) (67) (23) (69) (69)
Hes5 ^−/−	Increased goblet cells	Not reported	Muc2, Dll1 and Fbw7β	(68)
Villin-Cre;Hes1 ^flox/ ; Hes3 ^–/ ;Hes5 ^–/–	Increased goblet, Paneth, enteroendocrine and cleaved caspase-3⁺ cell. Decreased Ki67⁺ cells.	Not reported	Not reported	(23)
Math1^β-Gal/- Math1^{Δintestine/Lacz} Math1^LoxP/LoxP/AHCre Atoh1^flox/flox:Fabp-Cre Atoh1^fl/fl;villin-cre^ER Lrig1^CreERT2/+;Atoh1^fl/fl	Decreased goblet, enteroendocrine and Paneth cells.	Lack of cryptdins	Not reported	(72) (76) (65) (78) (64) (75)

The name of each experimental mouse model is written as in the original article. The phenotype observed was based on histology, immunohistochemistry, Western analysis and flow cytometry. KO, knockout.