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Strain Name:

C3FeB6 A/Aw-J-Ankank/J

Stock Number:

000200

Availability:

Repository-Cryopreserved


General Terms and Conditions

Former Name      C3FeB6 A/Aw-J-ank/J    (Changed: 15-DEC-04 )
Genes & Alleles   A;   Aw-J;   Ank;   Ankank;   a;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Spontaneous Mutation
Specieslaboratory mouse
Background Strain C3FeB6
Donor Strain JGBF F15
GenerationN32 F2p

Appearance
agouti with stiff feet
Related Genotype: A/A Ankank/Ankank

white-bellied agouti with stiff feet
Related Genotype: A/Aw-J Ankank/Ankank

agouti, unaffected
Related Genotype: A/A +/?

white-bellied agouti, unaffected
Related Genotype: A/Aw-J +/? or Aw-J/Aw-J +/?

Strain Description
The progressive ankylosis allele (ank) is a spontaneous recessive mutation that causes a severe phenotype of joint calcification and degeneration. Few homozygotes survive beyond 5 months of age, although the adults can breed. Generally no more than 2 litters are produced by homozygotes of either sex. At 4 or 5 weeks of age, homozygotes can be identified by their inability to grasp a wire cage lid with their front paws when suspended above it. The joints swell with a milky fluid, and undergo a process proceeding through mononuclear inflammatory infiltration, hydroxyapatite deposition and increased calcification, hyperplasia, and fibrous and bony ankylosis. (for details see Mahowald et al., 1989; Hakim et al., 1984; Sweet and Green, 1981.) The front feet are affected before the hind feet and the phenotype is more severe in the most distal joints of the limbs. Hyperplasia and degeneration of the joint tissues, and ankylosis occur progressively, decreasing mobility and resulting in a rigid, crouched posture in the adult. Their gate becomes slow, halting, and flatfooted. The morphological changes underlying the stiffening of the vertebral column and resulting thoracic kyphosis are detailed by Sampson, 1988a and 1988b, and Sampson et al., 1991.

There is an immune cell involvement in the joints secondary to the central defect. Treatment of ank/ank mice with hydrocortisone beginning at 5 weeks of age resulted in reduced synovial and subsynovial hyperplasia, reduced growth of cartilaginous and bony bridges, and increased accumulation of intra-articular apatite possibly due to the reduction in macrophage activity (Hakim et al., 1986.). Reconstitution of wild type mice with bone marrow or spleen cells from ank/ank mice does not transfer disease and reconstitution of ank/ank mice with wild type bone marrow or spleen cells does not prevent disease (Krug et al., 1997). Additionally, there is an immune cell defect. There is a reduction in the response of spleen cells to phytohaemagglutinin or concanavalin A although the response to LPS appears normal. Spleen cells or macrophages from ank/ank mice do not suppress normal spleen cell responses to phytohaemagglutinin and wild type spleen cells or macrophages do not restore phytohaemagglutinin responsiveness to spleen cells from ank/ank mice (Krug et al., 1989). Fibroblasts from ank/ank mice are Hyperproliferative in response to transforming growth factor beta 1 (Krug, 1998). No impact was found on the phenotype of ank/+ or ank/ank mice when transgenic HLA-B27 was co-expressed (Krug and Taurog, 2000).

In addition to progressive ankylosis and calcification of the peripheral joints and axial skeleton, homozygotes have a smaller overall body size, and some develop balanitis, priapism, and scaling skin lesions on the plantar surface of the paws. The hypermineralization phenotype is associated with abnormal inorganic pyrophophate levels and the downregulation of osteopontin (Harmey et al., 2004).

Strain Development
The progressive ankylosis mutation arose spontaneously in the strain JGBF/Le (Stock No. 000260), a balanced stock for jagged tail (jg) and buff (bf). An affected female displaying a flat-footed gait with rigid toes was the founder for the ank strain. This female's progeny were bred onto a C3FeB6 background via an outcross-intercross breeding scheme. Thus homozygotes were bred to C3FeB6F1 then their obligate heterozygous offspring were sibling mated to produce homozygous breeders for the next generation. The initial characterization was done on N5F1 mice. In June 1976 this strain was at N6, in early 1979 it was at N11, and in November 1983 it reached N24. Neither jg nor bf have been found in this strain since N2. C3FeB6-A/Aw-J-ank was frozen in 1987 by breeding N32 homozygotes to C3FeB6-A/Aw-J to get heterozygous N33 embryos.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Ankank/Ankank

        involves: JGBF jg Vps33abf
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:6580)
    • death by 5 months of age
  • skeleton phenotype
  • abnormal cartilage morphology (MGI Ref ID J:6580)
    • increased calcium deposit in calcified cartilage
  • abnormal joint mobility (MGI Ref ID J:122727)
    • joint mobility is decreased at 6 weeks and is more severe at 12 weeks similar to in Anktm1.1Kng homozygotes
    • reduction in joint mobility in the forelimb joints are more severe than in the hindlimbs and distal joint in the hindlimbs are more severely affected than proximal joints
  • abnormal joint morphology (MGI Ref ID J:6580)
    • stiffness of joints starting in forefeet and toes, quickly spreading to other joints
    • bone volume is significantly increased and increases in severity with time
  • craniofacial phenotype
  • abnormal tooth hard tissue morphology (MGI Ref ID J:122727)
    • the calcified materials surrounding the neck and tooth of all 12 molars is increased
    • the neck thickness relative to the enamel cap width is increased
    • abnormal cementum morphology (MGI Ref ID J:122727)
      • at 12 weeks, enlargement of the cementum
  • reproductive system phenotype
  • reduced female fertility (MGI Ref ID J:6580)
    • do not produce more than two litters
  • reduced male fertility (MGI Ref ID J:6580)
    • do not produce more than two litters

Ankank/Ankank

        involves: C3HeB/FeJ * C57BL/6J * JGBF/LeJ
  • homeostasis/metabolism phenotype
  • abnormal ion homeostasis (MGI Ref ID J:63420)
    • primary skin fibroblast cultures show an increase in intracellular and a decrease in extracellular pyrophosphate indicative of defective phosphate homeostatis, and this defect is corrected by transfection with wildtype Ank
  • immune system phenotype
  • arthritis (MGI Ref ID J:63420)
    • histology of the digit joints shows narrowing of the joint spaces, erosion of cartilage, accumulation of debris, and ectopic calcification
  • skeleton phenotype
  • abnormal cartilage morphology (MGI Ref ID J:63420)
  • abnormal joint mobility (MGI Ref ID J:63420)
    • wean age homozygotes are unable to grasp a wire cage tope due to stiffness in the digits
  • abnormal joint morphology (MGI Ref ID J:63420)
  • arthritis (MGI Ref ID J:63420)
    • histology of the digit joints shows narrowing of the joint spaces, erosion of cartilage, accumulation of debris, and ectopic calcification
  • joint calcification (MGI Ref ID J:63420)

Gene & Allele Details

Allele Symbol A
Allele Name wild type
Gene Symbol and Name a, nonagouti
Chromosome 2
Gene Common Name(s) AGSW; AGTI; AGTIL; ASP; As; MGC126092; MGC126093; SHEP9; agouti; agouti signal protein; agouti suppressor;
 
Allele Symbol Aw-J
Allele Name white bellied agouti Jackson
Common Name(s) AWJ;
Strain of OriginC57BL/6J
Gene Symbol and Name a, nonagouti
Chromosome 2
Gene Common Name(s) AGSW; AGTI; AGTIL; ASP; As; MGC126092; MGC126093; SHEP9; agouti; agouti signal protein; agouti suppressor;
 
Allele Symbol Ankank
Allele Name progressive ankylosis
Common Name(s) ank;
Strain of OriginJGBF jg Vps33a
Gene Symbol and Name Ank, progressive ankylosis
Chromosome 15
Gene Common Name(s) CCAL2; CMDJ; CPPDD; D15Ertd221e; DNA segment, Chr 15, ERATO Doi 221, expressed; FLJ27166; HANK; MANK; mKIAA1581;
General Note Development of the joint disorder studied in the joints of the forefeet is characterized by an initial distention of joints with a milky fluid containing large macrophage-like mononuclear cells and suspended calcium hydroxyapatite, accompanied by proliferation of the synovial cells with subsequent roughness of the cartilaginous articular surfaces and eventual fusion of the articular cartilages, and by formation of periarticular cartilage bridges with subsequent ossification leading to complete joint fusion. The Ank disease resembles calcium hydroxyapatite-associated arthropathies in man although it is considerably more severe (J:7672).Light and electron microscopic studies of homozygous mutant mice mice show limb joint changes similar to human ankylosing spondylitis (OMIM 106300) (J:23576). Intervertebral disks are extensively mineralized with depositions of hydroxyapatite crystals, also resembling ankylosing spondylitis (J:751).
Molecular Note A single nucleotide G to T substitution is predicted to result in a substitution at codon 440 from Glu to a stop codon in the encoded protein. [MGI Ref ID J:63420]

Control Information

  Allele   Control
 Ankank  +/? sibling
 Ankank  001203 C3FeB6F1/J A/Aw-J
 
  Considerations for Choosing Controls

Genotyping Protocols

Aw-J

Related Strains

View Strains carrying   A     (17 strains)

View Strains carrying   Aw-J     (31 strains)

Strains carrying other alleles of a
000251   AEJ.Cg-ae +/a Gdf5bp-H/J
000202   AEJ/Gn-bd/J
000199   AEJ/GnLeJ
000427   B10.CE-H13b Aw/(30NX)SnJ
000420   B10.LP-H13b Aw/Sn
000477   B10.PA-Pldnpa H3e at/SnJ
000419   B10.UW-H3b we Pax1un at/SnJ
003879   B10;TFLe-a/a T tf/+ tf/J
001538   B6 x B6C3Sn a/A-T(1;9)27H/J
000916   B6 x B6C3Sn a/A-T(5;12)31H/J
000602   B6 x B6C3Sn a/A-T(8;16)17H/J
000618   B6 x FSB/GnEi a/a Ctslfs/J
000577   B6 x STOCK a Oca2p Hps5ru2 Ednrbs/J
000601   B6 x STOCK a/a T(7;18)50H/J
000592   B6 x STOCK T(2;4)13H a/J
000769   B6.C/(HZ18)By-at-44J/J
000001   B6.C3 A/a Mgrn1md/J
000203   B6.C3-Aiy/a/J
000017   B6.C3Fe-Avy/J
005505   B6.Cg-Ay Slc7a11sut/LmLlp
000021   B6.Cg-Ay/J
001572   B6.Cg-am-J/J
000785   B6;D2-a Es1e/J
000604   B6C3 a/A-T(10;13)199H +/+ Lystbg-J/J or Lystbg-2J/J
002807   B6C3Fe a/a-Meox2fla/J
000224   B6C3Fe a/a-Scyl1mdf/J
001037   B6C3Fe a/a-Agtpbp1pcd/J
000221   B6C3Fe a/a-Alx4lst-J/J
002062   B6C3Fe a/a-Atp7aMo-8J/J
001756   B6C3Fe a/a-Cacng2stg/J
001815   B6C3Fe a/a-Col1a2oim/J
000231   B6C3Fe a/a-Csf1op/J
000209   B6C3Fe a/a-Dh/J
000211   B6C3Fe a/a-Dstdt-J/J
000210   B6C3Fe a/a-Edardl-J/J
000207   B6C3Fe a/a-Edaraddcr/J
000182   B6C3Fe a/a-Eef1a2wst/J
001278   B6C3Fe a/a-Glra1spd/J
000241   B6C3Fe a/a-Glrbspa/J
002875   B6C3Fe a/a-Hoxd13spdh/J
000304   B6C3Fe a/a-Krt71Ca Scn8amed-J/J
000226   B6C3Fe a/a-Largemyd/J
000636   B6C3Fe a/a-Lmx1adr-J/J
001280   B6C3Fe a/a-Lse/J
001573   B6C3Fe a/a-MitfMi/J
001035   B6C3Fe a/a-Napahyh/J
000181   B6C3Fe a/a-Otogtwt/J
000278   B6C3Fe a/a-Papss2bm Hps1ep Hps6ru/J
000205   B6C3Fe a/a-Papss2bm/J
002078   B6C3Fe a/a-Pcdh15av-2J/J
000246   B6C3Fe a/a-Pitpnavb/J
001430   B6C3Fe a/a-Ptch1mes/J
000506   B6C3Fe a/a-Qkqk/J
000235   B6C3Fe a/a-Relnrl/J
000237   B6C3Fe a/a-Rorasg/J
000290   B6C3Fe a/a-Sox10Dom/J
000230   B6C3Fe a/a-Tcirg1oc/J
003612   B6C3Fe a/a-Trak1hyrt/J
001512   B6C3Fe a/a-Ttnmdm/J
001607   B6C3Fe a/a-Unc5crcm/J
000005   B6C3Fe a/a-Wc/J
000243   B6C3Fe a/a-Wnt1sw/J
000248   B6C3Fe a/a-Xpl/J
001750   B6C3Fe a/a-XsJ/J
000624   B6C3Fe a/a-anx/J
003020   B6C3Fe a/a-dep/J
002018   B6C3Fe a/a-din/J
002339   B6C3Fe a/a-nma/J
000240   B6C3Fe a/a-soc/J
000063   B6C3Fe a/a-sy/J
001055   B6C3Fe a/a-tip/J
000245   B6C3Fe a/a-tn/J
000065   B6C3Fe a/a-we Pax1un at/J
000296   B6C3Fe-a/a Hoxa13Hd Mcoln3Va-J/J
000019   B6C3Fe-a/a-Itpr1opt/J
001022   B6C3FeF1/J a/a
000971   B6EiC3 a/A-Och/J
000551   B6EiC3 a/A-Tbx15de-H/J
006450   B6EiC3 a/A-Vss/J
000557   B6EiC3-+ a/LnpUl A/J
000503   B6EiC3Sn a/A-Gy/J
001811   B6EiC3Sn a/A-Otcspf-ash/J
002343   B6EiC3Sn a/A-Otcspf/J
000391   B6EiC3Sn a/A-Pax6Sey-Dey/J
001924   B6EiC3Sn a/A-Ts(1716)65Dn
001923   B6EiC3Sn a/A-Ts(417)2Lws Tim/J
000225   C3FeLe.B6 a/a-Ptpn6me/J
000198   C3FeLe.B6-a/J
000291   C3FeLe.Cg-a/a Hm KitlSl Krt71Ca-J/J
001272   C3H/HeSnJ-Ahvy/J
000099   C3HeB/FeJ-Avy/J
001886   C3HeB/FeJLe a/a-gnd/J
000584   C57BL/6J-+ T(1;2)5Ca/a +/J
000258   C57BL/6J-Ai/a/J
000774   C57BL/6J-Asy/a/J
000055   C57BL/6J-at-33J/J
000070   C57BL/6J-atd/J
000284   CWD/LeJ
000670   DBA/1J
000671   DBA/2J
001057   HPT/LeJ
000260   JGBF/LeJ
002468   KK.Cg-Ay/J
000262   LS/LeJ
000265   MY/HuLeJ
000308   SSL/LeJ
001427   STOCK Aw us/J
000994   STOCK a Myo5ad Mregdsu/J
000064   STOCK a Tyrp1b Sisi/J
002238   STOCK a Tyrp1b shmy/J
001433   STOCK a skt/J
000579   STOCK a tp/J
000319   STOCK a us/J
002648   STOCK a/a Cln6nclf/J
000317   STOCK a/a Egfrwa2/J
000302   STOCK a/a MitfMi-wh +/+ Itpr1opt/J
000286   STOCK a/a Myo5ad fd/+ +/J
000206   STOCK a/a Tyrc-h/J
001432   STOCK a/a Tyrp1b sks/Tyrp1b +/J
000281   STOCK a/a ma ft/ma ft/J
000312   STOCK stb + a/+ Fignfi a/J
000596   STOCK T(2;11)30H/+ x AEJ-a Gdf5bp-H/J or A/J-a Gdf5bp-J/J
000970   STOCK T(2;16)28H A/T(2;16)28H a/J
000590   STOCK T(2;4)1Sn a/J
000594   STOCK T(2;8)26H a/T(2;8)26H a Tyrp1+/Tyrp1b/J
000623   TR/DiEiJ
View Strains carrying other alleles of a     (126 strains)

Research Applications

This mouse can be used to support research in many areas including:

Ankank related

Dermatology Research
Skin and Hair Texture Defects

Developmental Biology Research
Growth Defects Growth Defects (homozygous)
Skeletal Defects

Immunology and Inflammation Research
Immunodeficiency Associated with Other Defects
Inflammation

Mouse/Human Gene Homologs
craniometaphyseal dysplasia, autosomal dominant

References

Selected Reference(s)

Hakim FT; Brown KS; Oppenheim JJ. 1986. 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 29(1):114-23. [PubMed: 3004514]  [MGI Ref ID J:109949]

Hakim FT; Cranley R; Brown KS; Eanes ED; Harne L; Oppenheim JJ. 1984. Hereditary joint disorder in progressive ankylosis (ank/ank) mice. I. Association of calcium hydroxyapatite deposition with inflammatory arthropathy. Arthritis Rheum 27(12):1411-20. [PubMed: 6095872]  [MGI Ref ID J:7672]

Ho AM; Johnson MD; Kingsley DM. 2000. Role of the mouse ank gene in control of tissue calcification and arthritis [see comments] Science 289(5477):265-70. [PubMed: 10894769]  [MGI Ref ID J:63420]

Krug HE. 1998. Fibroblasts from mice with progessive ankylosis proliferate excessively in response to transforming growth factor-beta 1. J Investig Med 46(4):134-9. [PubMed: 9635372]  [MGI Ref ID J:109902]

Krug HE; Mahowald ML; Clark C. 1989. Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. III. Proliferative spleen cell response to T cell mitogens. Clin Exp Immunol 78(1):97-101. [PubMed: 2805429]  [MGI Ref ID J:109935]

Krug HE; Taurog JD. 2000. HLA-B27 has no effect on the phenotypic expression of progressive ankylosis in ank/ank mice J Rheumatol 27(5):1257-9. [PubMed: 10813297]  [MGI Ref ID J:62431]

Krug HE; Wietgrefe MM; Ytterberg SR; Taurog JD; Mahowald ML. 1997. Murine progressive ankylosis is not immunologically mediated. J Rheumatol 24(1):115-22. [PubMed: 9002021]  [MGI Ref ID J:109905]

Mahowald ML; Krug H; Halverson P. 1989. Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. II. Light and electron microscopic findings. J Rheumatol 16(1):60-6. [PubMed: 2541245]  [MGI Ref ID J:23576]

Nurnberg P; Thiele H; Chandler D; Hohne W; Cunningham ML; Ritter H; Leschik G; Uhlmann K; Mischung C; Harrop K; Goldblatt J; Borochowitz ZU; Kotzot D; Westermann F; Mundlos S; Braun HS; Laing N; Tinschert S. 2001. Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia. Nat Genet 28(1):37-41. [PubMed: 11326272]  [MGI Ref ID J:69128]

Reichenberger E; Tiziani V; Watanabe S; Park L; Ueki Y; Santanna C; Baur ST; Shiang R; Grange DK; Beighton P; Gardner J; Hamersma H; Sellars S; Ramesar R; Lidral AC; Sommer A; Raposo do Amaral CM; Gorlin RJ; Mulliken JB; Olsen BR. 2001. Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet 68(6):1321-6. [PubMed: 11326338]  [MGI Ref ID J:109879]

Sampson HW. 1988. Ultrastructure of the mineralizing metacarpophalangeal joint of progressive ankylosis (ank/ank) mice. Am J Anat 182(3):257-69. [PubMed: 3213824]  [MGI Ref ID J:109941]

Sampson HW. 1988. Spondyloarthropathy in progressive ankylosis (ank/ank) mice: morphological features. Spine 13(6):645-9. [PubMed: 3175755]  [MGI Ref ID J:109942]

Sampson HW; Davis RW; Dufner DC. 1991. Spondyloarthropathy in progressive ankylosis mice: ultrastructural features of the intervertebral disk. Acta Anat (Basel) 141(1):36-41. [PubMed: 1659102]  [MGI Ref ID J:751]

Sweet HO; Green MC. 1981. Progressive ankylosis, a new skeletal mutation in the mouse. J Hered 72(2):87-93. [PubMed: 7276519]  [MGI Ref ID J:6580]

Additional References

Price and Supply Information

Strain Name: C3FeB6 A/Aw-J-Ankank/J
Stock Number: 000200

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Mouse Mutant Resource collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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