Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta

Hart, Patricia; Hart, Thomas C.; Michalec, Michael; Ryu, Ok Hee; Simmons, Darrin; Hong, Sung Pil; Wright, J. Timothy

doi:10.1136/jmg.2003.017657

Cited by 239 publications

(220 citation statements)

References 40 publications

Supporting

Mentioning

207

Contrasting

Unclassified

Order By: Relevance

“…Eventually it was demonstrated that two proteases are involved: matrix metalloproteinase 20 (Bartlett et al, 1996) and kallikrein 4 . These enzymes undoubtedly play critical roles in dental enamel formation, as mutations in MMP20 and KLK4 cause autosomal recessive amelogenesis imperfecta (Hart et al, 2004;Kim et al, 2005;Ozdemir et al, 2005;Papagerakis et al, 2008). The functions of MMP-20 and KLK4 are best explained in the context of how enamel forms.…”

Section: Dental Enamelmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

221

190

View full text Add to dashboard Cite

Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin . The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

show abstract

Section: Dental Enamelmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

221

190

View full text Add to dashboard Cite

show abstract

“…Eight of these genes have also been associated with anomalies in tooth development. All five genes previously identified as causing amelogenesis imperfecta, a disease characterized by enamel defects (Aldred et al, 2003), when disrupted, are present within these 29 genes: amelogenin (Amelx; Lagerstrom et al, 1991), kallikrein 4 (Klk4; Hart et al, 2004), matrix metalloproteinase 20 (MMP20; enamelysin; Ozdemir et al, 2005), enamelin (Enam; Rajpar et al, 2001), and distal-less homeobox 3 (Dlx3; Price et al, 1999). Other genes present included ameloblastin (Ambn), a gene that when inactivated in the mouse presents with a similar enamel phenotype (Paine et al, 2003), as well as the dentin sialophosphoprotein (Dspp) gene associated with dentinogenesis imperfecta (Zhang et al, 2001) and the paired-like homeodomain transcription factor 2 (Pitx2) associated with Rieger Syndrome (Semina et al, 1996).…”

Section: Microarray Analysis Of Mouse Molar Tooth Gene Expressionmentioning

confidence: 99%

Identification of novel genes expressed during mouse tooth development by microarray gene expression analysis

Pemberton

Oka

et al. 2007

Developmental Dynamics

View full text Add to dashboard Cite

To identify genes heretofore undiscovered as critical players in the biogenesis of teeth, we have used microarray gene expression analysis of the developing mouse molar tooth (DMT) between postnatal day (P) 1 and P10 to identify genes differentially expressed when compared with 16 control tissues. Of the top 100 genes exhibiting increased expression in the DMT, 29 were found to have been previously associated with tooth development. Differential expression of the remaining 71 genes not previously associated with tooth development was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. Further analysis of seven of the latter genes by mRNA in situ hybridization found that five were specific to the developing tooth in the craniofacial region (Rspo4, Papln, Amtn, Gja1, Maf). Of the remaining two, one was found to be more widely expressed (Sp7) and the other was found to be specific to the nasal serous gland, which is close to, but distinct from, the developing tooth (Vrm). Developmental Dynamics 236: 2245-2257, 2007.

show abstract

“…Mutational analysis has initially focused on genes encoding enamel matrix proteins, identifying mutations in amelogenin (AMELX; Kim et al, 2004), enamelin (ENAM; Kang et al, 2009), kallikrein 4 (KLK4; Hart et al, 2004) and enamelysin (MMP20; Kim et al, 2005b). Genetic analysis-such as linkage analysis, autozygosity mapping, and exome sequencing-has recently identified mutations in the family with sequence similarity 83 member H (FAM83H; Kim et al, 2008), WD repeat-containing protein 72 (WDR72; El-Sayed et al, 2009;Lee et al, 2010), family with sequence similarity 20 member A (FAM20A; O'Sullivan et al, 2011;Cho et al, 2012), chromosome 4 open reading frame 26 (C4orf26; Parry et al, 2012), solute carrier family 24 member 4 (SLC24A4; Parry et al, 2013), laminin beta 3 (LAMB3; Kim et al, 2013;Poulter et al, 2014b), and integrin beta 6 (ITGB6; Poulter et al, 2014a;Wang et al, 2014).…”

mentioning

confidence: 99%

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

et al. 2014

View full text Add to dashboard Cite

Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal formation and elongation should be well controlled to achieve an exceptional hardness and a compact microstructure. Enamel matrix calcification occurs with several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among them, amelogenin is the most abundant enamel matrix protein, and multiple isoforms resulting from extensive but wellconserved alternative splicing and postsecretional processing have been identified. In this report, we recruited a family with a unique enamel defect and identified a silent mutation in exon 4 of the AMELX gene. We show that the mutation caused the inclusion of exon 4, which is almost always skipped, in the mRNA transcript. We further show, by generating and characterizing a transgenic animal model, that the alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization.

show abstract

Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta

Cited by 239 publications

References 40 publications

Functions of KLK4 and MMP-20 in dental enamel formation

Functions of KLK4 and MMP-20 in dental enamel formation

Identification of novel genes expressed during mouse tooth development by microarray gene expression analysis

Alteration of Conserved Alternative Splicing in AMELX Causes Enamel Defects

Contact Info

Product

Resources

About