Table 1.
Cleft palate-related ECM gene mutation in human and mice.
| Gene | Protein | Human Disease | Cleft palate related Clinal features | References | Mouse mutation | Mouse mutation phenotypes | References |
|---|---|---|---|---|---|---|---|
| COL2A1 | Col II | Stickler syndrome type 1 (OMIM 108300) | Cleft palate or bifid uvula, | 26,109-111 | Transgenic Del1 mice carrying six copies of with COL2A1 (Del) mutation with a 150-bp deletion containing the 45-bp exon 7 and intro7: | Craniofacial ossification retarded; reduced cartilage and bone growth; cleft palate; | 38 |
| Kniest dysplasia (OMIM 156550) | Cleft palate | 111 | Transgenic mice with targeted inactivation of the COL2A1 gene | No endochondral bone or epiphyseal growth plate in long bones with normal membranous and periosteal skeleton | 34 | ||
| Platyspondyly lethal skeletal dysplasia (OMIM 151210) | No cleft palate | 111 | ENU induced mutation has a G to A transition at Chromosome 15:97815207, which causes a premature stop codon at amino acid 645 | Cleft palate; shortened nose | 112 | ||
| COL11A1 | Col XI | Stickler syndrome type 2 (OMIM 604841) |
Cleft palate | 110 | Deletion of a cytidine residue about 570 nt downstream of the translation initiation codon in COL11A1 (cho) mRNA causes a reading frame shift and introduces a premature stop codon | Cleft palate, shortened head and mandible, short limbs, protruding tongue | 39,40 |
| Marshall syndrome (OMIM 154780) |
Cleft palate | 26 | |||||
| COL11A2 | Col XI | Stickler syndrome type 3: (OMIM 184480) |
Cleft palate | 110 | Full-length Col11a2 chain was unable to occur because of the presence of premature termination codons | NO cleft palate; Hearing loss, smaller size, shorter snout, skeletal abnormalities including abnormal cranium morphology and long bone epiphyseal plate |
41,42 |
| Nance-Insley syndrome (OMIM 215150) |
Cleft palate | 41 | |||||
| FN1 | Fibronectin | NR | Conditional knock out FN1 in cranial neural crest cells | Cleft palate, abnormal cardiac morphogenesis, thymus development defects | 48 | ||
| Conditional knock out FN1 in mesoderm cells | Cleft palate, abnormal cardiac morphogenesis, thymus development defects, edema, etc. | 47 | |||||
| TNXB | Tenascin-X | Tenascin-X deficiency (OMIM 606408) |
Bifid uvula | 55,56,113,114 | NR | ||
| ACAN | Aggrecan | NR | Gene mutation in ACAN: cmd/cmd (cartilage matrix defieciency), 7-bp deletion in exon 5; cmd-Bc, spontaneous mutation, complete loss of exons 2-18 |
Cleft palate, short limbs, tail, and snout | 115,116 | ||
| VCAN | Versican | NR | Haploinsufficiendy of Versican in Adamts20 mutant mice (Vcanhdf/+;Adamts20bt/bt) | 65% mutant exhibited cleft palate | 12 |
NR, not reported.