Maturation stage enamel malformations in Amtn and Klk4 null mice

Stephanie M. Núñez, Yong Hee P. Chun, Bernhard Ganss, Yuanyuan Hu, Amelia S. Richardson, James E. Schmitz, Roberto Fajardo, Jie Yang, Jan C.C. Hu, James P. Simmer

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


Amelotin (AMTN) and kallikrein-4 (KLK4) are secreted proteins specialized for enamel biomineralization. We characterized enamel from wild-type, Amtn-/-, Klk4-/-, Amtn+/-Klk4+/- and Amtn-/-Klk4-/- mice to gain insights into AMTN and KLK4 functions during amelogenesis. All of the null mice were healthy and fertile. The mandibular incisors in Amtn-/-, Klk4-/- and Amtn-/-Klk4-/- mice were chalky-white and chipped. No abnormalities except in enamel were observed, and no significant differences were detected in enamel thickness or volume, or in rod decussation. Micro-computed tomography (μCT) maximum intensity projections localized the onset of enamel maturation in wild-type incisors distal to the first molar, but mesial to this position in Amtn-/-, Klk4-/- and Amtn-/-Klk4-/- mice, demonstrating a delay in enamel maturation in Amtn-/- incisors. Micro-CT detected significantly reduced enamel mineral density (2.5 and 2.4 gHA/cm3) in the Klk4-/- and Amtn-/-Klk4-/- mice respectively, compared with wild-type enamel (3.1 gHA/cm3). Backscatter scanning electron microscopy showed that mineral density progressively diminished with enamel depth in the Klk4-/- and Amtn-/-Klk4-/- mice. The Knoop hardness of the Amtn-/- outer enamel was significantly reduced relative to the wild-type and was not as hard as the middle or inner enamel. Klk4-/- enamel hardness was significantly reduced at all levels, but the outer enamel was significantly harder than the inner and middle enamel. Thus the hardness patterns of the Amtn-/- and Klk4-/- mice were distinctly different, while the Amtn-/-Klk4-/- outer enamel was not as hard as in the Amtn-/- and Klk4-/- mice. We conclude that AMTN and KLK4 function independently, but are both necessary for proper enamel maturation.

Original languageEnglish (US)
Pages (from-to)219-233
Number of pages15
JournalMatrix Biology
StatePublished - May 1 2016


  • Ameloblasts
  • Amelotin
  • Kallikrein-4
  • Knoop hardness
  • Null mice
  • μCT

ASJC Scopus subject areas

  • Molecular Biology


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