Phenotypes associated with this allele

• Allele Symbol: Ank^ank
• Allele Name: progressive ankylosis
• Allele ID: MGI:1856651
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ank^ank/Ank^ank	involves: BALB/c * C3H * C57BL/6 * JGBF/Le	MGI:4354513
hm2	Ank^ank/Ank^ank	involves: C3HeB/FeJ * C57BL/6J * JGBF/LeJ	MGI:2655174
hm3	Ank^ank/Ank^ank	Not Specified	MGI:4367727

Genotype
MGI:4354513

hm1

• Allelic Composition: Ank^ank/Ank^ank
• Genetic Background: involves: BALB/c * C3H * C57BL/6 * JGBF/Le

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

skeleton

abnormal osteoblast physiology ( J:111462 )

• osteoblasts exhibit hypercalcification compared with wild-type cell

• however, hypercalcification in osteoblasts can be reversed by soluble Enpp1 and Spp1

cardiovascular system

calcified aorta ( J:110028 )

• aortic media exhibit calcification and chondrogenic differentiation unlike wild-type aortas

cellular

abnormal osteoblast physiology ( J:111462 )

• osteoblasts exhibit hypercalcification compared with wild-type cell

• however, hypercalcification in osteoblasts can be reversed by soluble Enpp1 and Spp1

Genotype
MGI:2655174

hm2

• Allelic Composition: Ank^ank/Ank^ank
• Genetic Background: involves: C3HeB/FeJ * C57BL/6J * JGBF/LeJ

mortality/aging

premature death ( J:6580 )

• few mutants survive beyond 5 months of age

growth/size/body

abnormal tooth hard tissue morphology ( 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 ( J:122727 )

• at 12 weeks, enlargement of the cementum

decreased body weight ( J:6580 )

• lower body weight, first noticeable between 10 and 20 days of age

reproductive system

reduced female fertility ( J:6580 )

♀ • do not produce more than two litters

reduced male fertility ( J:6580 )

♂ • do not produce more than two litters

skeleton

autoimmune arthritis ( J:63420 )

• histology of the digit joints shows narrowing of the joint spaces, erosion of cartilage, accumulation of debris, and ectopic calcification

abnormal skeleton morphology ( J:6580 )

• progressive ankylosis

abnormal tooth hard tissue morphology ( 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 ( J:122727 )

• at 12 weeks, enlargement of the cementum

abnormal femur morphology ( J:168526 )

• metaphyseal trabeculae reduced in both thickness and number

abnormal sesamoid bone of gastrocnemius morphology ( J:6580 )

• some of the sesamoid bones are enlarged and appear to be fused with the nearest long bone

abnormal tendon morphology ( J:6580 )

• degeneration in many, although not all, tendons associated with affected joints

calcified tendon ( J:6580 )

• some calcification in the tendons around the shoulder joint at 11 weeks of age

kyphosis ( J:6580 )

• adults exhibit thoracic kyphosis and prominent haunches

abnormal cartilage morphology ( J:6580 , J:63420 )

• degeneration and increase in calcification in the cartilage (J:6580)

• cartilage erosion (J:63420)

abnormal joint morphology ( J:6580 , J:63420 , J:122727 )

• mutants develop a noninflammatory degenerative joint disease, with stiffness of joints starting in forefeet and toes, quickly spreading to other joints (J:6580)

• mutants show increased numbers of osteoblast-like cells in the synovial membrane of joints and excessive amount of fibrous tissue, cartilage, and bone in joints at later stages, with many areas of cystic necrosis (J:6580)

• synovial lining in most places, except over articular cartilage or ligament, has a thickened surface layer (J:6580)

• necrosis in the fibrous tissue of the joints, including the ligaments and cartilage (J:6580)

• joint space narrowing, accumulation of debris in the joint space, and ectopic calcification in and around the affected joints (J:63420)

• bone volume in joints is significantly increased and increases in severity with time (J:122727)

abnormal transverse acetabular ligament morphology ( J:6580 )

• calcification of the transverse acetabular ligament, which bridges the acetabular notch of the hip, is seen at 17 weeks of age

abnormal synovial joint cavity morphology ( J:6580 )

• reduction in the size of the joint cavities in the forefoot at 33 days of age, with excessive osteoblasts

• the joint cavity of the shoulder appears shrunken and opaque, with some calcification in the tendons around the joint at 11 weeks of age

calcified joint ( J:6580 , J:63420 )

• abnormal and increased calcification within some of the joints (knee, elbow, vertebral column) and joint cavities, resulting in calcified masses at various places near joints (J:6580)

• ectopic calcification in and around the affected joints (J:63420)

fused joints ( J:6580 )

• progressive akylosis, such that by 17 weeks of age, the joints of the foot, including the wrist, and of the ribs with adjacent sternebrae are completely ankylosed

• fore and hind feet at 31 weeks of age have toe bones that show bony and cartilaginous fusions across the joints, usually including the sesamoid bones

abnormal ligament morphology ( J:6580 )

• degeneration in many, although not all, ligaments associated with affected joints

• calcification of the transverse acetabular ligament, which bridges the acetabular notch of the hip, is seen at 17 weeks of age

decreased joint mobility ( J:6580 , J:63420 , J:122727 , J:168526 )

• progressive loss of mobility of the joints occurs with age; stiffening of the joints is first apparent at 4-5 weeks of age in the forefeet and eventually involves all the joints of the limbs and vertebral column (J:6580)

• when lifted by the tail from a wire grid, 4.5-5 week old mutants are unable to cling to the grid as the toes are very rigid (J:6580)

• wean age homozygotes are unable to grasp a wire cage tope due to stiffness in the digits (J:63420)

• joint mobility is decreased at 6 weeks and is more severe at 12 weeks similar to in Ank^tm1.1Kng homozygotes (J:122727)

• 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 (J:122727)

• stiffness of joints observed at 4-5 weeks of age (J:168526)

muscle

abnormal tendon morphology ( J:6580 )

• degeneration in many, although not all, tendons associated with affected joints

calcified tendon ( J:6580 )

• some calcification in the tendons around the shoulder joint at 11 weeks of age

craniofacial

abnormal tooth hard tissue morphology ( 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 ( J:122727 )

• at 12 weeks, enlargement of the cementum

behavior/neurological

decreased grip strength ( J:168526 )

• unable to grab cage bars at 4-5 weeks of age

abnormal posture ( J:6580 )

• adults exhibit a rigid posture

abnormal gait ( J:6580 )

• slow halting gait, with all feet flat against the surface

limbs/digits/tail

abnormal limb morphology ( J:6580 )

• in the limbs, abnormalities are more severe in the distal than proximal joints and in the forelimbs than in the hindlimbs

abnormal digit morphology ( J:6580 )

• toes of the forefeet are stiff and flattened at 33 and 35 days of age, while these abnormalities occur later in the hindfeet (11-17 weeks of age)

abnormal transverse acetabular ligament morphology ( J:6580 )

• calcification of the transverse acetabular ligament, which bridges the acetabular notch of the hip, is seen at 17 weeks of age

abnormal femur morphology ( J:168526 )

• metaphyseal trabeculae reduced in both thickness and number

abnormal sesamoid bone of gastrocnemius morphology ( J:6580 )

• some of the sesamoid bones are enlarged and appear to be fused with the nearest long bone

homeostasis/metabolism

abnormal ion homeostasis ( 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

autoimmune arthritis ( J:63420 )

• histology of the digit joints shows narrowing of the joint spaces, erosion of cartilage, accumulation of debris, and ectopic calcification

Genotype
MGI:4367727

hm3

• Allelic Composition: Ank^ank/Ank^ank
• Genetic Background: Not Specified

skeleton

abnormal intervertebral disk morphology ( J:751 )

• EM analysis shows accumulation of electron-dense crystals aligned along collagen fibers; mitochondria of some cells have a high affinity for calcium phosphate crystals

• in some disk regions cartilage is so heavily mineralized that mineral deposists extend beyond the extracellular matrix over cell cytoplasm

• ossification of intervertebral disk space is common

calcified intervertebral disk ( J:751 )

• crystals are in the form of calcium hydroxyapatite

abnormal chondrocyte morphology ( J:751 )

• 6-8 week old affected mice have chondrocytes with numerous large vacuoles and abnormal condensations of glycogen