AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity

Tian Liang, Yuanyuan Hu, Charles E. Smith, Amelia S. Richardson, Hong Zhang, Jie Yang, Brent Lin, Shih Kai Wang, Jung Wook Kim, Yong-hee P Chun, James P. Simmer, Jan C.C. Hu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere929
JournalMolecular Genetics and Genomic Medicine
DOIs
StateAccepted/In press - Jan 1 2019

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Amelogenesis
Organ Specificity
Dental Enamel
Ameloblasts
Dentin
Mutation
Enamel Organ
Incisor
Minerals
Epithelium
Amelogenesis Imperfecta
Galactosidases
Amelogenin
Proteins
Oviducts
Nasal Mucosa
Seminal Vesicles
Submandibular Gland
Epididymis
Salivary Glands

Keywords

  • Ambn Amelx
  • amelin
  • ameloblastin
  • amelogenin
  • dental enamel formation
  • matrix proteins
  • mineralization
  • missense mutation
  • sheath protein
  • sheathlin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. / Liang, Tian; Hu, Yuanyuan; Smith, Charles E.; Richardson, Amelia S.; Zhang, Hong; Yang, Jie; Lin, Brent; Wang, Shih Kai; Kim, Jung Wook; Chun, Yong-hee P; Simmer, James P.; Hu, Jan C.C.

In: Molecular Genetics and Genomic Medicine, 01.01.2019.

Research output: Contribution to journalArticle

Liang, Tian ; Hu, Yuanyuan ; Smith, Charles E. ; Richardson, Amelia S. ; Zhang, Hong ; Yang, Jie ; Lin, Brent ; Wang, Shih Kai ; Kim, Jung Wook ; Chun, Yong-hee P ; Simmer, James P. ; Hu, Jan C.C. / AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. In: Molecular Genetics and Genomic Medicine. 2019.
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title = "AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity",
abstract = "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.",
keywords = "Ambn Amelx, amelin, ameloblastin, amelogenin, dental enamel formation, matrix proteins, mineralization, missense mutation, sheath protein, sheathlin",
author = "Tian Liang and Yuanyuan Hu and Smith, {Charles E.} and Richardson, {Amelia S.} and Hong Zhang and Jie Yang and Brent Lin and Wang, {Shih Kai} and Kim, {Jung Wook} and Chun, {Yong-hee P} and Simmer, {James P.} and Hu, {Jan C.C.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/mgg3.929",
language = "English (US)",
journal = "Molecular genetics & genomic medicine",
issn = "2324-9269",
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TY - JOUR

T1 - AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity

AU - Liang, Tian

AU - Hu, Yuanyuan

AU - Smith, Charles E.

AU - Richardson, Amelia S.

AU - Zhang, Hong

AU - Yang, Jie

AU - Lin, Brent

AU - Wang, Shih Kai

AU - Kim, Jung Wook

AU - Chun, Yong-hee P

AU - Simmer, James P.

AU - Hu, Jan C.C.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Ambn Amelx

KW - amelin

KW - ameloblastin

KW - amelogenin

KW - dental enamel formation

KW - matrix proteins

KW - mineralization

KW - missense mutation

KW - sheath protein

KW - sheathlin

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U2 - 10.1002/mgg3.929

DO - 10.1002/mgg3.929

M3 - Article

JO - Molecular genetics & genomic medicine

JF - Molecular genetics & genomic medicine

SN - 2324-9269

M1 - e929

ER -