title: Mouse genetic background influences the dental phenotype.
abstract: Dental enamel covers the crown of the vertebrate tooth and is considered to be the hardest tissue in the body. Enamel develops during secretion of an extracellular matrix by ameloblast cells in the tooth germ, prior to eruption of the tooth into the oral cavity. Secreted enamel proteins direct mineralization patterns during the maturation stage of amelogenesis as the tooth prepares to erupt. The amelogenins are the most abundant enamel proteins and are required for normal enamel development. Phenotypic differences were observed between incisors from individual Amelx (amelogenin) null mice that had a mixed 129xC57BL/6J genetic background and between inbred wild-type (WT) mice with different genetic backgrounds (C57BL/6J, C3H/HeJ, FVB/NJ). We hypothesized that this could be due to modifier genes, as human patients with a mutation in an enamel protein gene causing the enamel defect amelogenesis imperfecta (AI) can also have varied appearance of dentitions within a kindred. Enamel density measurements varied for all WT inbred strains midway during incisor development. Enamel thickness varied between some WT strains, and, unexpectedly, dentin density varied extensively between incisors and molars of all WT and Amelx null strains studied. WTFVB/NJ incisors were more similar to those of Amelx null mice than to those of the other WT strains in terms of incisor height/width ratio and pattern of enamel mineralization. Strain-specific differences led to the conclusion that modifier genes may be implicated in determining both normal development and severity of enamel appearance in AI mouse models and may in future studies be related to phenotypic heterogeneity within human AI kindreds reported in the literature.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pa., USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: William S
authors.initials: WS
authors.lastname: Konicki
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Wright
authors.forename: Cynthia
authors.initials: C
authors.lastname: Suggs
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kuehl
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism; D000566:Amelogenesis / Q000235:genetics*; D053523:Amelogenin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003743:Dental Enamel / Q000196:embryology*; D003746:Dental Enamel Proteins / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D007180:Incisor / Q000196:embryology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019228:Tooth Crown / Q000196:embryology*
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2065-9
references.pmid: 1848692
references.citation: Hum Mutat. 1995;5(3):251-9
references.pmid: 7599636
references.citation: J Biol Chem. 2001 Aug 24;276(34):31871-5
references.pmid: 11406633
references.citation: J Biol Chem. 2008 May 30;283(22):15056-62
references.pmid: 18390542
references.citation: Hum Mol Genet. 1994 May;3(5):827-8
references.pmid: 8081371
references.citation: Hum Mol Genet. 2001 Aug 1;10(16):1673-7
references.pmid: 11487571
references.citation: J Mech Behav Biomed Mater. 2008 Jan;1(1):18-29
references.pmid: 19627768
references.citation: Eur J Oral Sci. 2011 Dec;119 Suppl 1:70-4
references.pmid: 22243230
references.citation: Birth Defects Orig Artic Ser. 1971 Jun;7(7):153-84
references.pmid: 4375507
references.citation: Science. 2003 Aug 15;301(5635):967-9
references.pmid: 12920299
references.citation: Eur Arch Paediatr Dent. 2010 Aug;11(4):201-8
references.pmid: 20840832
references.citation: J Med Genet. 2005 Mar;42(3):271-5
references.pmid: 15744043
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004 Feb;97(2):220-30
references.pmid: 14970781
references.citation: Am J Hum Genet. 2012 Sep 7;91(3):565-71
references.pmid: 22901946
references.citation: J Med Genet. 2004 Jul;41(7):545-9
references.pmid: 15235027
references.citation: Bone. 2006 Dec;39(6):1283-9
references.pmid: 16920415
references.citation: J Dent Res. 2009 Apr;88(4):356-60
references.pmid: 19407157
references.citation: Hum Hered. 1988;38(4):189-206
references.pmid: 3169793
references.citation: Genomics. 2005 Jan;85(1):60-70
references.pmid: 15607422
references.citation: Am J Med Genet. 1997 Oct 17;72(2):197-204
references.pmid: 9382143
references.citation: Bone. 2005 Jan;36(1):111-22
references.pmid: 15664009
references.citation: Connect Tissue Res. 2003;44 Suppl 1:72-8
references.pmid: 12952177
references.citation: J Dent Res. 1982 Dec;Spec No:1467-71
references.pmid: 6958703
references.citation: Genomics. 1991 Aug;10(4):971-5
references.pmid: 1916828
references.citation: Hum Genet. 2008 Nov;124(4):357-68
references.pmid: 18784943
references.citation: Nature. 1968 Sep 21;219(5160):1253-4
references.pmid: 4877918
references.citation: Nat Rev Genet. 2001 Mar;2(3):165-74
references.pmid: 11256068
references.citation: J Exp Zool B Mol Dev Evol. 2009 Jul 15;312B(5):437-44
references.pmid: 19090561
references.citation: J Dent Res. 2013 Dec;92(12):1118-22
references.pmid: 24072097
references.citation: Clin Genet. 2010 Apr;77(4):306-13
references.pmid: 20132241
references.citation: Arch Oral Biol. 1993 Nov;38(11):945-55
references.pmid: 8297258
references.citation: ISRN Dent. 2013 Sep 16;2013:684607
references.pmid: 24159389
references.citation: J Dent Res. 2005 Nov;84(11):1031-5
references.pmid: 16246936
references.citation: J Dent Res. 2002 Nov;81(11):794-8
references.pmid: 12407097
references.citation: Cells Tissues Organs. 2009;189(1-4):224-9
references.pmid: 18714142
references.citation: Genomics. 1992 Nov;14(3):567-73
references.pmid: 1358807
references.citation: PLoS Genet. 2012;8(4):e1002644
references.pmid: 22511884
references.citation: Nat Genet. 2005 Nov;37(11):1175-80
references.pmid: 16254563
references.citation: J Dent Res. 2010 Feb;89(2):165-9
references.pmid: 20042744
references.citation: J Dent Res. 2011 May;90(5):552-60
references.pmid: 20929720
references.citation: Trends Genet. 2006 Dec;22(12):649-53
references.pmid: 17007958
references.citation: Curr Opin Genet Dev. 2003 Jun;13(3):290-5
references.pmid: 12787792
references.citation: Hum Mutat. 2008 Aug;29(8):E95-9
references.pmid: 18484629
references.citation: J Musculoskelet Neuronal Interact. 2002 Mar;2(3):225-31
references.pmid: 15758440
references.citation: ILAR J. 2006;47(2):132-40
references.pmid: 16547370
references.citation: J Biol Chem. 2008 Apr 18;283(16):10858-71
references.pmid: 18252720
references.citation: Bull Group Int Rech Sci Stomatol. 1969 Apr;12(2):151-207
references.pmid: 5255602
references.citation: J Dent Res. 2013 Oct;92(10):899-904
references.pmid: 23958762
references.citation: Proc R Soc Med. 1956 Oct;49(10):759-65
references.pmid: 13379391
references.citation: Am J Hum Genet. 2009 Nov;85(5):699-705
references.pmid: 19853237