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 Species laboratory mouse Background Strain C3FeB6 Donor Strain JGBF F15 Generation N32 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 |
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 Origin | C57BL/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 Origin | JGBF 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
Strains carrying A allele
003301 (C57BL/6J x C3H-Eya1bor)F1/J 002083 B6 x B6EiC3 a/A-T(7;16)235Dn/J 000507 B6 x B6EiC3 a/A-Otcspf/J 000628 B6.CE-A Amy1b Amy2b/J 004200 B6;CBACa Aw-J/A-Npr2cn-2J/J 000604 B6C3 a/A-T(10;13)199H +/+ Lystbg-J/J or Lystbg-2J/J 001752 B6CBCa Aw-J/A-T(7;15)9H/J 006450 B6EiC3 a/A-Vss/J 000557 B6EiC3-+ a/LnpUl A/J 000504 B6EiC3Sn a/A-Cacnb4lh/J 000553 B6EiC3Sn a/A-Egfrwa2 Wnt3avt/J 001811 B6EiC3Sn a/A-Otcspf-ash/J 002343 B6EiC3Sn a/A-Otcspf/J 001923 B6EiC3Sn a/A-Ts(417)2Lws Tim/J 000638 C3FeB6 A/Aw-J-Spnb4qv-J/J 000283 LT.CAST-A/J 001759 STOCK A Tyrc Sha/J View Strains carrying A (17 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)
Additional ReferencesHakim 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]
Price and Supply Information
| Strain Name: | C3FeB6 A/Aw-J-Ankank/J |
| Stock Number: | 000200 |
Price Details
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Supply Details
| Standard Supply | Repository-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. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
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