PAX6
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Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the PAX6 gene.[5]
Function
PAX6 is a member of the
Pax6 serves as a regulator in the coordination and pattern formation required for differentiation and proliferation to successfully take place, ensuring that the processes of
Species distribution
PAX6 protein function is highly conserved across
Genomic organisation of the PAX6 locus varies among species, including the number and distribution of
Of the four
Isoforms
The vertebrate PAX6 locus encodes at least three different protein
Clinical significance
Experiments in mice demonstrate that a deficiency in Pax-6 leads to decrease in brain size, brain structure abnormality leading to Autism, lack of iris formation or a thin cornea. [citation needed] Knockout experiments produced eyeless phenotypes reinforcing indications of the gene's role in eye development.[7]
Mutations
During embryological development the PAX6 gene, found on chromosome 2 in mice, can be seen expressed in multiple early structures such as the spinal cord, hindbrain, forebrain and eyes.[19] Mutations of the PAX6 gene in mammalian species can produce a drastic effect on the phenotype of the organism. This can be seen in mice that contain homozygous mutations of the 422 amino acid long transcription factor encoded by PAX6 in which they do not develop eyes or nasal cavities termed ‘small eye’ mice (PAX10sey/sey).[19][20] Deletion of PAX6 induces the same abnormal phenotypes indicating that mutations cause the protein to lose functionality. PAX6 is essential is the formation of the retina, lens and cornea due to its role in early cell determination when forming precursors of these structures such as the optic vesicle and overlying surface ectoderm.[20] PAX10 mutations also hinder nasal cavity development due to the similar precursor structures that in small eye mice do not express PAX10 mRNA.[21] Mice lacking any functional pax6 begin to be phenotypically differentiable from normal mouse embryos at about day 9 to 10 of gestation.[22] The full elucidation of the precise mechanisms and molecular components by which the PAX6 gene influences eye, nasal and central nervous system development are still researched however, the study of PAX6 has brought more understanding to the development and genetic complexities of these mammalian body systems.
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000007372 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027168 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 13736351.
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- ^ PMID 18322702.
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- ^ PMID 23359656.
- S2CID 15085580.
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- ^ PMID 8875254.
- ^ PMID 1687460.
- PMID 7789273.
- PMID 7559133.
Further reading
- Callaerts P, Halder G, Gehring WJ (1997). "PAX-6 in development and evolution". Annual Review of Neuroscience. 20 (1): 483–532. PMID 9056723.
- Prosser J, van Heyningen V (1998). "PAX6 mutations reviewed". Human Mutation. 11 (2): 93–108. S2CID 66974.
- Hever AM, Williamson KA, van Heyningen V (June 2006). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2". Clinical Genetics. 69 (6): 459–70. S2CID 5676139.
- Glaser T, Walton DS, Maas RL (November 1992). "Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene". Nature Genetics. 2 (3): 232–9. S2CID 26794244.
- Ton CC, Hirvonen H, Miwa H, Weil MM, Monaghan P, Jordan T, van Heyningen V, Hastie ND, Meijers-Heijboer H, Drechsler M (December 1991). "Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region" (PDF). Cell. 67 (6): 1059–74. S2CID 34641827.
- O'Donnell FE, Pappas HR (February 1982). "Autosomal dominant foveal hypoplasia and presenile cataracts. A new syndrome". Archives of Ophthalmology. 100 (2): 279–81. PMID 7065945.
- Martha A, Strong LC, Ferrell RE, Saunders GF (1995). "Three novel aniridia mutations in the human PAX6 gene". Human Mutation. 6 (1): 44–9. S2CID 33125924.
- Hanson I, Brown A, van Heyningen V (June 1995). "A new PAX6 mutation in familial aniridia". Journal of Medical Genetics. 32 (6): 488–9. PMID 7666404.
- Mirzayans F, Pearce WG, MacDonald IM, Walter MA (September 1995). "Mutation of the PAX6 gene in patients with autosomal dominant keratitis". American Journal of Human Genetics. 57 (3): 539–48. PMID 7668281.
- van Heyningen V, Little PF (1995). "Report of the fourth international workshop on human chromosome 11 mapping 1994". Cytogenetics and Cell Genetics. 69 (3–4): 127–58. PMID 7698003.
- Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B (February 1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". Comptes Rendus de l'Académie des Sciences, Série III. 318 (2): 263–72. PMID 7757816.
- Martha A, Ferrell RE, Mintz-Hittner H, Lyons LA, Saunders GF (May 1994). "Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins". American Journal of Human Genetics. 54 (5): 801–11. PMID 7909985.
- Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL (August 1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects". Nature Genetics. 7 (4): 463–71. S2CID 11622431.
- Epstein JA, Glaser T, Cai J, Jepeal L, Walton DS, Maas RL (September 1994). "Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing". Genes & Development. 8 (17): 2022–34. PMID 7958875.
- Davis A, Cowell JK (December 1993). "Mutations in the PAX6 gene in patients with hereditary aniridia". Human Molecular Genetics. 2 (12): 2093–7. PMID 8111379.
- Hanson IM, Fletcher JM, Jordan T, Brown A, Taylor D, Adams RJ, Punnett HH, van Heyningen V (February 1994). "Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly". Nature Genetics. 6 (2): 168–73. S2CID 12270847.
- Hanson IM, Seawright A, Hardman K, Hodgson S, Zaletayev D, Fekete G, van Heyningen V (July 1993). "PAX6 mutations in aniridia". Human Molecular Genetics. 2 (7): 915–20. PMID 8364574.
- Azuma N, Nishina S, Yanagisawa H, Okuyama T, Yamada M (June 1996). "PAX6 missense mutation in isolated foveal hypoplasia". Nature Genetics. 13 (2): 141–2. S2CID 22671179.
External links
- PAX6+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview
- GeneReviews/NCBI/NIH/UW entry on Aniridia
- OMIM entries on Aniridia
- Gene Expression Patterns from the Allen Brain Atlases
- Overview of all the structural information available in the PDB for UniProt: P26367 (Paired box protein Pax-6) at the PDBe-KB.