This gene is a member of thepaired box (PAX) family oftranscription factors. During mouseembryogenesis Pax9 expression starts from embryonic day 8.5 and becomes more evident by E9.5; at this stage its expression is restricted to the pharyngealendoderm.[8][9] Later on, Pax9 is also expressed in theaxial skeleton.[8] Pax9 is required for craniofacial, tooth and limb development,[7][8] and may more generally involve development ofstratified squamous epithelia as well as various organs andskeletal elements.[5] PAX9 plays a role in the absence ofwisdom teeth in some human populations (possibly along with the less well studiedAXIN2 andMSX1).[7]
This gene was found amplified inlung cancer. The amplification covers three tissue developmental genes -TTF1,NKX2-8, and PAX9.[10] It appears that certain lung cancer cells select for DNA copy number amplification and increased RNA/protein expression of these three coamplified genes for functional advantages.
Oligodontia is a genetic disorder caused by the mutation of the PAX9 gene. This disorder results in the congenital absence of 6 or more permanent teeth not includingwisdom teeth.[11] Also known as selective tooth agenesis (STHAG), it is the most common disorder in regard to human dentition, affecting a little less than one fourth of the population.[11] The gene PAX9 which can be found on chromosome 14 encodes a group of transcription factors that play an important role in early tooth development.[12] In humans, aframeshift mutation in the paired domain of PAX9 was discovered in those affected with oligodontia.[13] Multiple mechanisms are possible by which the mutation may arise. Recently, a study involving the missense mutation of a PAX9 gene suggests that the loss of function due to the absence DNA binding domain is a mechanism that causes oligodontia.[14] Those who express the PAX9 mutation and develop the disorder continue to have a normal life expectancy. Along with the mutation of the PAX9 gene, MSX1 gene mutations have also shown to affect dental development in fetuses.[14]
^Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M (April 1993). "Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9".Nature Genetics.3 (4):292–8.doi:10.1038/ng0493-292.PMID7981748.S2CID21338655.
^abStockton DW, Das P, Goldenberg M, D'Souza RN, Patel PI (January 2000). "Mutation of PAX9 is associated with oligodontia".Nature Genetics.24 (1):18–9.doi:10.1038/71634.PMID10615120.S2CID27526349.
^Chi N, Epstein JA (January 2002). "Getting your Pax straight: Pax proteins in development and disease".Trends in Genetics.18 (1):41–7.doi:10.1016/s0168-9525(01)02594-x.PMID11750700.
^Klein ML, Nieminen P, Lammi L, Niebuhr E, Kreiborg S (January 2005). "Novel mutation of the initiation codon of PAX9 causes oligodontia".Journal of Dental Research.84 (1):43–7.doi:10.1177/154405910508400107.PMID15615874.S2CID31928079.
^abJumlongras D, Lin JY, Chapra A, Seidman CE, Seidman JG, Maas RL, Olsen BR (February 2004). "A novel missense mutation in the paired domain of PAX9 causes non-syndromic oligodontia".Human Genetics.114 (3):242–9.doi:10.1007/s00439-003-1066-6.PMID14689302.S2CID12537564.
Kobielak A, Kobielak K, Wiśniewski AS, Mostowska A, Biedziak B, Trzeciak WH (2001). "The novel polymorphic variants within the paired box of the PAX9 gene are associated with selective tooth agenesis".Folia Histochemica et Cytobiologica.39 (2):111–2.PMID11374781.
Bannykh SI, Emery SC, Gerber JK, Jones KL, Benirschke K, Masliah E (July 2003). "Aberrant Pax1 and Pax9 expression in Jarcho-Levin syndrome: report of two Caucasian siblings and literature review".American Journal of Medical Genetics. Part A.120A (2):241–6.doi:10.1002/ajmg.a.20192.PMID12833407.S2CID1145497.
Peters H, Schuster G, Neubüser A, Richter T, Höfler H, Balling R (January 1997). "Isolation of the Pax9 cDNA from adult human esophagus".Mammalian Genome.8 (1):62–4.doi:10.1007/s003359900351.PMID9021154.S2CID26099337.
Stockton DW, Das P, Goldenberg M, D'Souza RN, Patel PI (January 2000). "Mutation of PAX9 is associated with oligodontia".Nature Genetics.24 (1):18–9.doi:10.1038/71634.PMID10615120.S2CID27526349.
Hetzer-Egger C, Schorpp M, Boehm T (July 2000). "Evolutionary conservation of gene structures of the Pax1/9 gene family".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression.1492 (2–3):517–21.doi:10.1016/s0167-4781(00)00130-5.PMID10899593.
Das P, Stockton DW, Bauer C, Shaffer LG, D'Souza RN, Wright T, Patel PI (April 2002). "Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia".Human Genetics.110 (4):371–6.doi:10.1007/s00439-002-0699-1.PMID11941488.S2CID8452.
Ikegawa S, Mabuchi A, Ogawa M, Ikeda T (June 2002). "Allele-specific PCR amplification due to sequence identity between a PCR primer and an amplicon: is direct sequencing so reliable?".Human Genetics.110 (6):606–8.doi:10.1007/s00439-002-0735-1.PMID12107448.S2CID34993937.
Gerber JK, Richter T, Kremmer E, Adamski J, Höfler H, Balling R, Peters H (July 2002). "Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus".The Journal of Pathology.197 (3):293–7.doi:10.1002/path.1115.PMID12115874.S2CID36999418.
Peck S, Peck L, Kataja M (December 2002). "Concomitant occurrence of canine malposition and tooth agenesis: evidence of orofacial genetic fields".American Journal of Orthodontics and Dentofacial Orthopedics.122 (6):657–60.doi:10.1067/mod.2002.129915.PMID12490878.
Mostowska A, Kobielak A, Biedziak B, Trzeciak WH (June 2003). "Novel mutation in the paired box sequence of PAX9 gene in a sporadic form of oligodontia".European Journal of Oral Sciences.111 (3):272–6.doi:10.1034/j.1600-0722.2003.00036.x.PMID12786960.
