Connexin mutant embryonic stem cells and human diseases

Table 1 Connexin knockout studies and human diseases

Mouse gene[1]	Mouse KO phenotypes	Human disease	Ref.
Cx231
Cx26	Embryonic lethality due to defective transplacental glucose uptake	Deafness; Skin disease	[14,68-70]
Cx29	No phenotype		[71]
Cx30	Hearing impairment; accelerated heart rate	Deafness; Skin disease	[31,68,72]
Cx30.2	Accelerated atrioventricular nodal conduction		[73]
Cx30.3	Difference in behavioral reactivity to vanilla scent	Skin disease	[69,74]
Cx312	Partial embryonic lethality due to a defect in early placental development	Deafness; Skin disease	[15,68,69,75]
Cx31.12	Partial embryonic lethality due to impaired placental development; Changed gene expression in the central nervous system		[16,76]
Cx32	Liver dysfunction; High incidence of liver tumors; Peripheral neuropathy	Charcot-Marie-Tooth disease	[36-38,40,77,78]
Cx331
Cx36	Loss of electrical coupling in interneurons of the neocortex; Disrupted rod pathways; Altered spontaneous firing patterns in the retina; Alterations in insulin secretion	Juvenile myoclonic epilepsy	[25,79-84]
Cx37	Female infertility; High bone mass		[11,85]
Cx39	Accelerated myogenesis and regeneration of skeletal muscle		[86]
Cx40	Cardiac conduction abnormalities; High incidence of cardiac malformations	Atrial standstill; Atrial fibrillation	[23,42,43,45,87,88]
Cx43	Early postnatal lethality due to cardiac malformation; Osteoblast dysfunction	Oculodentodigital dysplasia; Visceroatrial heterotaxia; Hypoplastic left heart syndrome; Atrial fibrillation	[10,52,55,67,89-94]
Cx45	Embryonic lethality due to cardiovascular defects; Altered spontaneous firing patterns in the retina		[12,25,44,53]
Cx46	Cataracts; Reduced heart rate and aberrant conduction along the His bundle branches	Cataract	[17,33,69]
Cx47	Myelin abnormalities	Pelizaeus–Merzbacher-like disease	[24,95-98]
Cx50	Microphthalmia and cataract	Cataract	[18,19,69]
Cx57	Reduction in horizontal cell receptive fields		[99,100]

¹No knockout (KO) studies have been reported for connexin (Cx) 23 and Cx33. Notably, however, the mouse small-eye mutant Aey12 has a point mutation in the Cx23 locus[101]. For Cx33, there is no orthologous gene in the human genome[1];

²About 60% (Cx31) and 30% (Cx31.1) of the embryos were lost in utero; the surviving adult mice were observed to have no morphological defects.