Sign up for a project by 15 Oct to get 15% off with Australian Spring Special!

AMBN Mutations Causing Hypoplastic Amelogenesis Imperfecta and Ambn knockout-NLS-lacZ Knockin Mice Exhibiting Failed Amelogenesis and Ambn Tissue-Specificity

 Back to publications


Mol Genet Genomic Med 2019 Sep;7(9):e929. doi: 10.1002/mgg3.929. Epub 2019 Aug 11.

AMBN Mutations Causing Hypoplastic Amelogenesis Imperfecta and Ambn knockout-NLS-lacZ Knockin Mice Exhibiting Failed Amelogenesis and Ambn Tissue-Specificity

T Liang;Y Hu;CE Smith;AS Richardson;H Zhang;J Yang;B Lin;SK Wang;JW Kim;YH Chun;JP Simmer;JCC Hu

Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan. Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Department of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, China. Department of Orofacial Sciences, UCSF School of Dentistry, San Francisco, California. Department of Dentistry, National Taiwan University School of Dentistry, Taipei City, Taiwan R.O.C. Department of Molecular Genetics and Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea. Department of Periodontics and Department of Cell Systems & Anatomy, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Service type: Knock-in mice


Background: Ameloblastin (AMBN) is a secreted matrix protein that is critical for the formation of dental enamel and is enamel-specific with respect to its essential functions. Biallelic AMBN defects cause non-syndromic autosomal recessive amelogenesis imperfecta. Homozygous Ambn mutant mice expressing an internally truncated AMBN protein deposit only a soft mineral crust on the surface of dentin. Methods: We characterized a family with hypoplastic amelogenesis imperfecta caused by AMBN compound heterozygous mutations (c.1061T>C; p.Leu354Pro/ c.1340C>T; p.Pro447Leu). We generated and characterized Ambn knockout/NLS-lacZ (AmbnlacZ/lacZ ) knockin mice. Results: No AMBN protein was detected using immunohistochemistry in null mice. ß-galactosidase activity was specific for ameloblasts in incisors and molars, and islands of cells along developing molar roots. AmbnlacZ/lacZ 7-week incisors and unerupted (D14) first molars showed extreme enamel surface roughness. No abnormalities were observed in dentin mineralization or in nondental tissues. Ameloblasts in the AmbnlacZ/lacZ mice were unable to initiate appositional growth and started to degenerate and deposit ectopic mineral. No layer of initial enamel ribbons formed in the AmbnlacZ/lacZ mice, but pockets of amelogenin accumulated on the dentin surface along the ameloblast distal membrane and within the enamel organ epithelia (EOE). NLS-lacZ signal was positive in the epididymis and nasal epithelium, but negative in ovary, oviduct, uterus, prostate, seminal vesicles, testis, submandibular salivary gland, kidney, liver, bladder, and bone, even after 15 hr of incubation with X-gal. Conclusions: Ameloblastin is critical for the initiation of enamel ribbon formation, and its absence results in pathological mineralization within the enamel organ epithelia.

View Publication