Table 1.

Mouse models used to study canonical Wnt signaling in mammary development and cancer

Mouse model	Structural modification	Mammary phenotype	References
MMTV-ΔN89-β-catenin	Stabilizing deletion of first 89 amino acids of β-catenin Luminal expression	Expansion K18+CD29hi 49flo Precocious alveologenesis Adenocarcinoma	[67,75]
MMTV-ΔN90-β-catenin	Stabilizing deletion of first 90 amino acids of β-catenin Luminal expression	Hyperplasia Adenocarcinoma	[90]
Catnb+/lox(ex3);WAP-Cre	Stabilizing deletion of Exon 3 (codons 5 to 80) of β-catenin	Squamous metaplasia	[93]
Catnb+/lox(ex3);MMTV-Cre	Luminal expression
MMTV-ΔN90-β-catenin x p53+/-	Stabilizing deletion of β-catenin on a p53 heterozygous background	Adenocarcinomas	[175]
	Luminal expression	Metastases
K5-ΔN57-β-catenin	Stabilizing deletion of first 57 amino acids of β-catenin Basal expression	Precocious development during pregnancy Hyperbranching Multiparous mice develop invasive basal-type carcinoma	[38,74]
MMTV-Wnt1	Wnt1 expression in luminal epithelia	Expansion of K14+, cd24+, cd29/49fhi basal stem cells Hyperbranching Adenocarcinoma	[33,67,84,85]
MMTV-Wnt10b	Expression of long isoform of Wnt10b in luminal epithelia	Precocious alveologenesis Hyperbranching Adenocarcinoma	[61]
MMTV-Lrp6	Expression of Lrp6 in luminal epithelia	Hyperplasia no tumors	[88]
ApcMin/+	Truncating mutation of APC at codon 850	Focal alveolar hyperplasias Mammary carcinomas (7 to 20% depending on strain background)	[178]
Apc+/1572	Truncating mutation of APC at codon 1572	Multifocal mammary adenocarcinomas (85.7%) Pulmonary metastases	[95]
K14-cre-Apc580/+	Truncating mutation of APC at codon 580 Basal expression	Mammary adenocarcinomas	[94]
BLG-Cre; Apc580S/580S	Truncating mutation of APC at codon 580 Luminal expression	Delayed ductal morphogenesis Metaplasia	[179]
MMTV-rtTA;TRE2-myc- tagged Axin-(IRES) GFP	Doxycycline-inducible Axin in luminal epithelia	Loss of alveologenesis	[76]
WAP-β-engrailed	β-engrailed expressed luminally	Failure to maintain alveoli	[77]
MMTV-β-engrailed		Lactation defect
Lrp5-/-	Loss of Lrp5	Loss of placodes Mild ductal hypoplasia Reduced regenerative capacity Resistant to Wnt-induced tumorigenesis	[34,39]
Lrp6-/-	Loss of Lrp6	Impaired sprouting, placode and fat pad development Decreased number of TEBs in heterozygotes	[40]
Wnt4-/-	Loss of Wnt4	Delayed side-branching	[69]
Wnt5a-/-	Loss of Wnt5a	Accelerated ductal morphogenesis	[64]
K5-rtTA/tetO-DKK1	Ectopic expression of Dkk1	Loss of mammary line and all placodal development	[36]
K14-Cre/Pygo2 flox	Loss of Pygo2 in mammary epithelium	Loss and small placodes Progressive loss of progenitor cell population	[38]
Pin1-/-	Loss of Pin1	Severe decrease in ductal and alveolar development during pregnancy	[80]
RANK-/-	Loss of RANK receptor	Loss of alveologenesis Failure to lactate Impaired side-branching in transplanted null outgrowths	[78,79]
Lef1-/-	Loss of Lef1	Impaired placodes Impaired bud morphogenesis	[37]
Rspo-/-	Loss of Rspo1	Defective side branching	[73]

APC, adenomatous polyposis coli; DKK, Dickkopf; GFP, green fluorescence protein; LRP, low-density lipoprotein-related protein; MMTV, mouse mammary tumor virus; Pygo2, pygopus homolog 2; RANK, receptor activator of NF-κB; TEB, terminal end bud; WAP, whey acidic protein.