Gene Symbol: Ank
Description: progressive ankylosis
Alias: Ankh, D15Ertd221e, ank, mKIAA1581, progressive ankylosis protein, fn54 protein
Species: mouse
Products:     Ank

Top Publications

  1. Reichenberger E, Tiziani V, Watanabe S, Park L, Ueki Y, Santanna C, et al. Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet. 2001;68:1321-6 pubmed
    ..performed, and we describe herein three different mutations, in five different families and in isolated cases, in ANK, a multipass transmembrane protein involved in the transport of intracellular pyrophosphate into extracellular ..
  2. Fong H, Foster B, Sarikaya M, Somerman M. Structure and mechanical properties of Ank/Ank mutant mouse dental tissues--an animal model for studying periodontal regeneration. Arch Oral Biol. 2009;54:570-6 pubmed publisher our studies focused on examining teeth obtained from mice with mutations at the mouse progressive ankylosis (ank) locus...
  3. Murshed M, Harmey D, Millan J, McKee M, Karsenty G. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev. 2005;19:1093-104 pubmed
  4. Harmey D, Hessle L, Narisawa S, Johnson K, Terkeltaub R, Millan J. Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders. Am J Pathol. 2004;164:1199-209 pubmed
    ..Mice deficient in NPP1 (Enpp1(-/-)), or defective in the PP(i) channeling function of ANK (ank/ank), have decreased levels of extracellular PP(i) and are hypermineralized...
  5. Johnson K, Goding J, van Etten D, Sali A, Hu S, Farley D, et al. Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. J Bone Miner Res. 2003;18:994-1004 pubmed
    ..PP(i) transport is modulated by the membrane channel protein ANK. Spontaneous articular cartilage calcification, increased vertebral cortical bone formation, and peripheral joint ..
  6. Gurley K, Reimer R, Kingsley D. Biochemical and genetic analysis of ANK in arthritis and bone disease. Am J Hum Genet. 2006;79:1017-29 pubmed
    Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly different skeletal phenotypes in mice and humans...
  7. Nurnberg P, Thiele H, Chandler D, Hohne W, Cunningham M, Ritter H, et al. Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia. Nat Genet. 2001;28:37-41 pubmed
    ..2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene...
  8. Ho A, Johnson M, Kingsley D. Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000;289:265-70 pubmed
    Mutation at the mouse progressive ankylosis (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction...
  9. Chen I, Wang C, Strecker S, Koczon Jaremko B, Boskey A, REICHENBERGER E. Introduction of a Phe377del mutation in ANK creates a mouse model for craniometaphyseal dysplasia. J Bone Miner Res. 2009;24:1206-15 pubmed publisher
    ..Mutations for autosomal dominant CMD have been identified in the progressive ankylosis gene ANKH. Previous studies of Ank loss-of-function models, Ank(null/null) and Ank(ank/ank) mice, suggest that Ank plays a ..

More Information


  1. Gurley K, Chen H, Guenther C, Nguyen E, Rountree R, Schoor M, et al. Mineral formation in joints caused by complete or joint-specific loss of ANK function. J Bone Miner Res. 2006;21:1238-47 pubmed
    ..A number of human mutations have subsequently been reported in the human ortholog (ANKH), some of which produce skull and long bone defects with no apparent defects in joints or articular cartilage...
  2. Villa Bellosta R, Wang X, Millan J, Dubyak G, O Neill W. Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle. Am J Physiol Heart Circ Physiol. 2011;301:H61-8 pubmed publisher
    ..contained mRNA for ectonucleotide pyrophosphatase/phosphodiesterases (NPP1-3), the putative PP(i) transporter ANK, and tissue-nonspecific alkaline phosphatase (TNAP)...
  3. Hakim F, Cranley R, Brown K, Eanes E, Harne L, Oppenheim J. Hereditary joint disorder in progressive ankylosis (ank/ank) mice. I. Association of calcium hydroxyapatite deposition with inflammatory arthropathy. Arthritis Rheum. 1984;27:1411-20 pubmed
    Progressive ankylosis (ank), a murine autosomal recessive mutation, produces an inflammatory joint disorder associated with intraarticular calcium hydroxyapatite deposition and culminates in fusion of the joints...
  4. Huang B, Takahashi K, Sakata T, Kiso H, Sugai M, Fujimura K, et al. Increased risk of temporomandibular joint closed lock: a case-control study of ANKH polymorphisms. PLoS ONE. 2011;6:e25503 pubmed publisher
    ..examination of the temporomandibular joint (TMJ) in ank mutant mice and to identify polymorphisms of the human ANKH gene in order to establish the relationship between the type of temporomandibular disorders (TMD) and ANKH ..
  5. Sampson H. Spondyloarthropathy in progressive ankylosis (ank/ank) mice: morphological features. Spine (Phila Pa 1976). 1988;13:645-9 pubmed
    ..These joints present a clear progression from syndesmophyte formation through joint bridging to total fusion. The similarities and differences of the disorder identified in this mouse and human spondyloarthropathies are discussed. ..
  6. Foster B, Ao M, Salmon C, Chavez M, Kolli T, Tran A, et al. Osteopontin regulates dentin and alveolar bone development and mineralization. Bone. 2018;107:196-207 pubmed publisher
    ..within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank-/-) mice, featuring reduced PPi, rapid cementogenesis, and excessive acellular cementum...
  7. Chen I, Wang L, Jiang X, Aguila H, REICHENBERGER E. A Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD). Hum Mol Genet. 2011;20:948-61 pubmed publisher
    ..A Phe377 (TTC(1130-1132)) deletion in exon 9 of the pyrophosphate (PPi) transporter ANK leads to CMD-like features in an Ank(KI/KI) mouse model...
  8. Wang J, Wang C, Tsui H, Las Heras F, Cheng E, Iscove N, et al. Microcytosis in ank/ank mice and the role of ANKH in promoting erythroid differentiation. Exp Cell Res. 2007;313:4120-9 pubmed
    Progressive ankylosis (Ank and the human homolog, ANKH) is a transmembrane protein which regulates transport of inorganic pyrophosphate (PPi)...
  9. Sasagawa S, Takemori H, Uebi T, Ikegami D, Hiramatsu K, Ikegawa S, et al. SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice. Development. 2012;139:1153-63 pubmed publisher
    ..These results demonstrate an essential role for SIK3 in facilitating chondrocyte hypertrophy during skeletogenesis and growth plate maintenance. ..
  10. Lieben L, Stockmans I, Moermans K, Carmeliet G. Maternal hypervitaminosis D reduces fetal bone mass and mineral acquisition and leads to neonatal lethality. Bone. 2013;57:123-31 pubmed publisher
    ..In conclusion, these data indicate that high maternal 1,25(OH)2D levels are transferred across the placental barrier and adversely affect the total amount of calcium stored in fetal bones which is accompanied by neonatal death. ..
  11. Minashima T, Quirno M, Lee Y, Kirsch T. The role of the progressive ankylosis protein (ANK) in adipogenic/osteogenic fate decision of precursor cells. Bone. 2017;98:38-46 pubmed publisher
    The progressive ankylosis protein (ANK) is a transmembrane protein that transports intracellular pyrophosphate (PPi) to the extracellular milieu...
  12. Mahowald M, Krug H, Halverson P. Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. II. Light and electron microscopic findings. J Rheumatol. 1989;16:60-6 pubmed
    ..These pathologic changes are the same as those found in the human spondyloarthropathies. Our EM findings demonstrate that hydroxyapatite crystals appear in the joints of ank/ank mice after the initial inflammatory phase.
  13. Li B, Ababon M, MATTESON P, Lin Y, Nanda V, Millonig J. Congenital Cataract in Gpr161vl/vl Mice Is Modified by Proximal Chromosome 15. PLoS ONE. 2017;12:e0170724 pubmed publisher
    ..of C3H/MOLF polymorphisms, and the biological relevancy of the genes in the interval identified three genes (Cdh6, Ank and Trio) that likely contribute to the rescue of the lens phenotype...
  14. Chen I, Tadinada A, Dutra E, Utreja A, Uribe F, Reichenberger E. Dental Anomalies Associated with Craniometaphyseal Dysplasia. J Dent Res. 2014;93:553-8 pubmed publisher
    ..consequences of orthodontic movement in a mouse model carrying a CMD knock-in (KI) mutation (Phe377del) in the Ank gene. All patients have a history of delayed eruption of permanent teeth...
  15. Carr G, Sayer J, Simmons N. Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem. 2007;20:507-16 pubmed
    Mutation of the pyrophosphate transporter, ANK, results in progressive arthritis in mice. ANK is expressed in non-skeletal tissues including kidney...
  16. Sampson H, Davis R, Dufner D. Spondyloarthropathy in progressive ankylosis mice: ultrastructural features of the intervertebral disk. Acta Anat (Basel). 1991;141:36-41 pubmed
    Progressive ankylosis mice (ank/ank) spontaneously develop a joint disorder characterized by calcium hydroxyapatite deposition and bony ankylosis of the joints of the axial and the appendicular skeleton...
  17. Johnson K, Yao W, Lane N, Naquet P, Terkeltaub R. Vanin-1 pantetheinase drives increased chondrogenic potential of mesenchymal precursors in ank/ank mice. Am J Pathol. 2008;172:440-53 pubmed publisher
    ..and intramembranous ectopic bone formation is mediated by extracellular PP(i) deficiency that develops in ank/ank mice...
  18. Rodrigues T, Nagatomo K, Foster B, Nociti F, Somerman M. Modulation of phosphate/pyrophosphate metabolism to regenerate the periodontium: a novel in vivo approach. J Periodontol. 2011;82:1757-66 pubmed publisher
    ..The progressive ankylosis protein (ANK) regulates the transport of PP(i), and progressive ankylosis gene (Ank) and knock-out (KO) mice ..
  19. Foster B, Nagatomo K, Bamashmous S, Tompkins K, Fong H, Dunn D, et al. The progressive ankylosis protein regulates cementum apposition and extracellular matrix composition. Cells Tissues Organs. 2011;194:382-405 pubmed publisher
    ..Factors increasing PP(i) include progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) while tissue nonspecific alkaline ..
  20. Dy P, Wang W, Bhattaram P, Wang Q, Wang L, Ballock R, et al. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell. 2012;22:597-609 pubmed publisher
  21. Khavandgar Z, Poirier C, Clarke C, Li J, WANG N, McKee M, et al. A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization. J Cell Biol. 2011;194:277-89 pubmed publisher
    ..Our data suggest tissue-specific roles for nSMase2 in skeletal tissues. ..
  22. Carr G, Moochhala S, Eley L, Vandewalle A, Simmons N, Sayer J. The pyrophosphate transporter ANKH is expressed in kidney and bone cells and colocalises to the primary cilium/basal body complex. Cell Physiol Biochem. 2009;24:595-604 pubmed publisher
    b>ANKH encodes a putative pyrophosphate transporter named ANKH, which regulates tissue calcification. ANKH is a transmembrane protein with at least 8 predicted transmembrane domains...
  23. Krug H. Fibroblasts from mice with progessive ankylosis proliferate excessively in response to transforming growth factor-beta 1. J Investig Med. 1998;46:134-9 pubmed
    ..a spontaneous arthropathy that produces ankylosis of peripheral and spinal joints in mice homozygous for the gene ank. This animal model bears a striking resemblance clinically, radiographically, and histologically to ankylosing ..
  24. Krug H, Taurog J. HLA-B27 has no effect on the phenotypic expression of progressive ankylosis in ank/ank mice. J Rheumatol. 2000;27:1257-9 pubmed
    ..a single-gene autosomal recessive mouse model of ankylosing spondylitis that arises in mice homozygous for the ank gene...
  25. Mahowald M, Krug H, Taurog J. Progressive ankylosis in mice. An animal model of spondylarthropathy. I. Clinical and radiographic findings. Arthritis Rheum. 1988;31:1390-9 pubmed
    ..We conclude that progressive ankylosis is a systemic disease with many clinical and radiographic similarities to human spondylarthropathies, and it may represent a useful animal model for the study of the human diseases. ..
  26. Krug H, Mahowald M, Clark C. Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. III. Proliferative spleen cell response to T cell mitogens. Clin Exp Immunol. 1989;78:97-101 pubmed
    Murine progressive ankylosis is a spontaneous disorder of mice resulting from a homozygous recessive genetic defect (ank/ank) which produces an inflammatory arthritis of peripheral and axial joints eventually resulting in ankylosis of ..
  27. Sohn P, Crowley M, Slattery E, Serra R. Developmental and TGF-beta-mediated regulation of Ank mRNA expression in cartilage and bone. Osteoarthritis Cartilage. 2002;10:482-90 pubmed
    b>Ank encodes a transmembrane protein that is involved in pyrophosphate (PPi) transport and mutations in the Ank gene have been associated with pathological mineralization in cartilage and bone...
  28. Foster B, Nagatomo K, Nociti F, Fong H, Dunn D, Tran A, et al. Central role of pyrophosphate in acellular cementum formation. PLoS ONE. 2012;7:e38393 pubmed publisher
    ..alkaline phosphatase, Alpl/TNAP), and those that increase local PP(i) and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1)...
  29. Johnson K, Polewski M, van Etten D, Terkeltaub R. Chondrogenesis mediated by PPi depletion promotes spontaneous aortic calcification in NPP1-/- mice. Arterioscler Thromb Vasc Biol. 2005;25:686-91 pubmed
    ..Similar changes were demonstrated in aortic SMCs from ank/ank mice, which are extracellular PP(i)-depleted because of defective ANK transmembrane PP(i) transport activity...
  30. Krug H, Wietgrefe M, Ytterberg S, Taurog J, Mahowald M. Murine progressive ankylosis is not immunologically mediated. J Rheumatol. 1997;24:115-22 pubmed
    ..The gene responsible for progressive ankylosis, ank, has not been identified and its product is unknown...
  31. Sweet H, Green M. Progressive ankylosis, a new skeletal mutation in the mouse. J Hered. 1981;72:87-93 pubmed
    Progressive ankylosis, ank, a new recessive skeletal mutation causing a noninflammatory joint disease in mice is described...
  32. Kirsch T, Kim H, Winkles J. Progressive ankylosis gene (ank) regulates osteoblast differentiation. Cells Tissues Organs. 2009;189:158-62 pubmed publisher
    The progressive ankylosis gene (ank) is a transmembrane protein that transports intracellular pyrophosphate to the extracellular milieu...
  33. Zaka R, Dion A, Kusnierz A, Bohensky J, Srinivas V, Freeman T, et al. Oxygen tension regulates the expression of ANK (progressive ankylosis) in an HIF-1-dependent manner in growth plate chondrocytes. J Bone Miner Res. 2009;24:1869-78 pubmed publisher
    The proximal promoter region of ANK, a gene that codes for a protein that regulates the transport of inorganic pyrophosphate, contains two hypoxia responsive elements (HREs); therefore, we studied the expression and function of ANK at ..
  34. Yuki K, Eva M, Richer E, Chung D, Paquet M, Cellier M, et al. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant. PLoS ONE. 2013;8:e55331 pubmed publisher
    ..This study illustrates that the regulation of Hamp and iron balance are crucial in the host response to Salmonella infection in Ank1 mutants. ..
  35. Hakim F, Brown K, Oppenheim J. Hereditary joint disorder in progressive ankylosis (ank/ank) mice. II. Effect of high-dose hydrocortisone treatment on inflammation and intraarticular calcium hydroxyapatite deposits. Arthritis Rheum. 1986;29:114-23 pubmed
    ..When affected (ank/ank) mice were treated with high doses of hydrocortisone, synovitis receded, development of cartilaginous and bony ..
  36. Neunaber C, Catala Lehnen P, Beil F, Marshall R, Kanbach V, Baranowsky A, et al. Increased trabecular bone formation in mice lacking the growth factor midkine. J Bone Miner Res. 2010;25:1724-35 pubmed publisher the molecular level, we performed a genome-wide expression analysis of primary osteoblasts and identified Ank and Enpp1 as Mdk-induced genes whose decreased expression in Mdk-deficient osteoblasts may explain, at least in ..
  37. Karlsson J, Johannesson M, Lindvall T, Wernhoff P, Holmdahl R, Andersson A. Genetic interactions in Eae2 control collagen-induced arthritis and the CD4+/CD8+ T cell ratio. J Immunol. 2005;174:533-41 pubmed
    ..Furthermore, the expression of CD86 on stimulated macrophages is linked to Eae2...
  38. Jin C, Frayssinet P, PELKER R, Cwirka D, Hu B, VIGNERY A, et al. NLRP3 inflammasome plays a critical role in the pathogenesis of hydroxyapatite-associated arthropathy. Proc Natl Acad Sci U S A. 2011;108:14867-72 pubmed publisher
    ..air-pouch model of synovitis, and they show decreased joint pathology accompanying spontaneous HA deposition in the ank-deficient mouse model of arthritis...
  39. Sampson H. Ultrastructure of the mineralizing metacarpophalangeal joint of progressive ankylosis (ank/ank) mice. Am J Anat. 1988;182:257-69 pubmed
    ..Synovial crystal phagocytosis was also observed. The progressive ankylosis mouse should be an important model for studying both crystal deposition and abnormal articular cartilage calcification. ..
  40. Seaman S, Stevens J, Yang M, Logsdon D, Graff Cherry C, St Croix B. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell. 2007;11:539-54 pubmed
    ..These studies reveal striking differences between physiological and pathological angiogenesis potentially important for the development of tumor-specific, vascular-targeted therapies. ..
  41. Dutra E, Chen I, Reichenberger E. Dental abnormalities in a mouse model for craniometaphyseal dysplasia. J Dent Res. 2013;92:173-9 pubmed publisher
    Mice carrying a knock-in mutation (Phe377del) in the Ank gene replicate many skeletal characteristics of human craniometaphyseal dysplasia, including hyperostotic mandibles...
  42. Kamogawa J, Terada M, Mizuki S, Nishihara M, Yamamoto H, Mori S, et al. Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains. Arthritis Rheum. 2002;46:1067-74 pubmed
    ..To clarify the mode of inheritance and the genome origins of arthritis in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr (MRL/lpr)...
  43. Sheen C, Kuss P, Narisawa S, Yadav M, Nigro J, Wang W, et al. Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification. J Bone Miner Res. 2015;30:824-36 pubmed publisher
    ..This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target. ..
  44. Kim H, Minashima T, McCarthy E, Winkles J, Kirsch T. Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling. J Bone Miner Res. 2010;25:1771-83 pubmed publisher
    The progressive ankylosis gene (ank) encodes a transmembrane protein that transports intracellular inorganic pyrophosphate (PP(i)) to the extracellular milieu...