this matrix in a controlled fashion and regulating
the ion concentration of the mineralizing environment. Many
of these processes are controlled directly by the ameloblasts,
the cells that produce enamel. There are many excellent reviews
written on enamel formation for those seeking further information
on this topic [22-25]
There are thousands, to potentially over 10,000 genes involved
in the formation of human enamel. We estimate from our research
on forming teeth using microarrays that the number is 10,000
or more genes are involved in tooth formation. Many of the
genes known to be involved in tooth formation can be reviewed
Genes involved in enamel formation are expressed in a highly
regulated fashion at specific times and locations. Genes produce
proteins that regulate gene expression, cell function and
can be secreted from the enamel forming cells (ameloblasts)
to form the matrix or template for the developing enamel.
Some of the proteins secreted from ameloblasts regulate the
size, shape and orientation of the growing enamel crystallites
and thus contribute to the ultimate structure and composition
of the enamel. Several genes and gene products that are either
known to be associated with AI or are thought to be likely
candidate genes for AI types where the associated gene remains
to be identified are briefly reviewed in the following sections.
Amelogenin: (product of AMELX and AMELY
genes located on the X and Y chromosomes) is the most abundant
protein in developing enamel [26,
27]. While its exact role in enamel formation is not fully
understood, it is thought to be crucial for regulating the
size and shape of the mineralizing enamel crystallites. Multiple
human mutations in the AMELX gene are associated
with different AI types. There are no known AMELY mutations
and it is thought that only about 10% of amelogenin mRNA transcripts
comes from the AMELY gene. A transgenic mouse lacking
expression of the AMELX gene has only a very thin
covering of enamel that lacks a prismatic structure that is
similar in appearance to some humans having AMELX
Ameloblastin: (product of AMBN gene located on chromosome
4) is another enamel associated protein that appears to be
the second most abundant enamel matrix protein .
The function of this protein is unknown but it is considered
a likely candidate for being associated with some AI types.
Enamelin: (product of ENAM gene located on chromosome
4) is secreted by amelobasts in relatively low amounts [30,
31]. It has been speculated that this protein could interact
with amelogenin or other enamel matrix proteins and be important
in determining growth of the length of enamel crystallites.
Multiple mutations ENAM gene mutations are associated
with different autosomally inherited AI types.
Enamelysin: (MMP20 gene located on chromosome 11)
is a proteinase that cleaves amelogenin and is thought to
be the major proteinase involved in processing the enamel
matrix proteins [32, 33].
The enamelysin knockout mouse has a reduced enamel thickness,
poorly mineralized enamel and the enamel lacks a prismatic
Kalikryn 4: (KLK4 gene located on chromosome 19)
is a proteinase that is secreted predominantly during the
maturation stage of enamel development .
This aggressive proteinase could be responsible for processing
any proteins not cleaved by enamelysin. Removal of this protein
during maturation is critical to allow the enamel crystallites
to grow and mature fully and the enamel to mineralize completely.
Mutation of KLK4 is associated with autosomal recessive
hypomaturation AI that is characterized by poorly mineralized
There are other enamel related genes, such as tuftelin, that
have been proposed as candidate genes for AI .
It is highly probable that genes not yet even known to be
important in enamel formation are associated with one or more
of the AI types where the molecular defect is not yet known.
FAM83H: (Product of FAM83H gene
located on chromosome 8q24). FAM83H is the first ameloblast
associated protein to be identified that is not secreted into
the extracellular matrix and is causative of AI. The are several
potential functions of this gene including Phospholipase D
(PLD)activity due to the genes similarities to the PLD gene.
Mutations in this gene can cause a severe disturbance in the
enamel mineralization (autosomal dominant hypocalcified AI
- ADHCAI). The actual function of this gene remains unknown
at this time.
For more information on genes in teeth link to http://bite-it.helsinki.fi/.