Table 3.

Knockout mouse models featuring esophageal atresia and/or tracheo-esophageal fistula, with phenotype associated with inactivation of counterpart human gene for comparison.

Mouse gene	Lung/foregut phenotype	Phenotype (other)	Reference	Human gene	Locus	Mutations	Lung/foregut phenotype	Phenotype (other)	Reference
Shh	Esophageal atresia, tracheo-esophageal fistula, lung anomalies	Abnormalities of CNS; cyclopia; distal limb truncation; abnormalities of axial skeleton, renal agenesis, abnormalities of heart looping, intestinal malrotation, annular pancreas, duodenal stenosis, intestinal transformation of the stomach, abnormal gut innervation, imperforate anus	[9,29,46]	SHH	7q36	YES	NR	Holoprosencephaly [HPE3, OMIM 142945], microphthalmia [OMIM 611638]	[40,48]
Foxf1	Esophageal atresia, tracheo-esophageal fistula, lung lobe fusion defects, pulmonary vascular defects	Axial skeletal defects	[22,35]	FOXF1	16q24.1	YES	Alveolar capillary dysplasia	Intestinal malrotation, atrio-ventricular canal defect, renal malformations	[52]
Gli2	Gli2−/− mice are normal. Gli2−/− Gli3+/− mice have esophageal atresia tracheo-esophageal fistula. Gli2−/− Gli3−/− mice have absent oesophagus, trachea and lungs	NR	[39]	GLI2	2q14	YES	NR	Holoprosencephaly	[47]
Gli3	See Gli2 entry	Gli3−/− mice are allelic with Xt. They have synpolydactyly and brain malformations.	[39]	GLI3	7p13	YES	NR	Greig cephalopolysyndactyly syndrome [GCPS, OMIM 175700]; Pallister–Hall syndrome [PHS, OMIM 146510] (imperforate anus, polydactyly, hypopituitarism, hypothalamic hamartoblastoma)	[20]
Noggin	Esophageal atresia, tracheo-esophageal fistula	Failure of closure of neural tube, exencephaly, wide, club-shaped limbs, shortened, abnormal body axis, lethality at birth	[27,43]	NOGGIN	17q22	YES	NR	Proximal symphalangism with multiple synostoses; stapes ankylosis with broad thumbs and toes; brachydactyly type B2	[4,17,26]
Sox2	Esophageal atresia, tracheo-esophageal fistula	Neurodegeneration, impaired neurogenesis	[13,44]	SOX2	3q26.3	YES	Esophageal atresia	Anophthalmia, genitourinary malformations	[59]

NR = not recorded.