A SPONTANEOUS ANKLE DEFORMITY I N A N INBRED STRAIN OF MOUSE MARKWALTON* Institute of Orthopaedics, Stunmore, Middlesex, England
PLATESCXV
AND
CXVI
THEknee joints of STR/ORT mice are prone to develop degenerative joint disease (osteoarthrosis) especially in the males (Walton, 1977a, b and c). During examination of the hind legs of these mice, some were observed to have swollen ankles or an abnormal angulation between the plane of the foot and the calf. An investigation into this ankle deformity is reported here. MATERIALS AND METHODS A visual inspection was made of the ankles of both male and female STRjORT mice in a colony of 400-500 individuals. This was repeated on a smaller colony of non-arthrosis prone CBA/ORT mice (Walton, 1977a and b). Normally the calcaneum lies with its long axis in the same plane as the sole of the foot and forms an acute angle to the long axis of the tibia. Ankles which deviated from this normal form or which had soft tissue swelling were examined radiographically. For this a Picker X-ray unit was used with a 1.0 mm aluminium filter and set at 25 kV and 30 mA for an exposure of 3 s. Lateral views were taken of the ankles with the animals under halothane/NzO anaesthesia. For the protection of the animal the remainder of its body was covered by a lead shield. Having recognised a skeletal abnormality in most of these mice a review was carried out of all the post-mortem radiographs taken of STR/ORT and CBA/ORT mice during the course of a previous study (Walton, 1977a). These had been produced using a Raymax 50 X-ray unit which has a 1.5 mm focal point and a 2.0 mm beryllium filter. Exposure had been for 40 s at 30 kV and 6 mA using Kodak Industrex M film. In addition, Spalteholz preparations stained with Alizarin Red S, also produced during the previous study, were examined. A serial survey was made of 30 male STR/ORT newborn mice. Every 2 mth, over a period of 14 mth, radiographs were taken of lateral views of their ankles with the mice under anaesthesia and using the Picker equipment.
RESULTS Gross appearances A. Living animals. In the mouse the calcaneum is a particularly long bone which extends the plane of the foot and forms a definite angulation with the Achilles tendon. The earliest gross indication of a deformity was a slight elevation of the posterior end of the heel, such that it no longer formed a continuation of the plane of the foot (fig. 1). This angulation could increase up to 45" after which the heel merely appeared abnormally rounded. Soft Received 9 Sept. 1917; accepted 16 Sept. 1911.
* Present address : Department of Orthopaedic Surgery, University of Otago Medical School,
PO Box 913, Dunedin, New Zealand. 3. PATH.-VOL.
124 (1978)
189
190
MARK WALTON
tissue changes did not necessarily accompany the deformity even in its extreme form. Occasionally, when soft tissue swelling had developed, large open or healing ulcers covered most of the weight-bearing surface of the heel. In almost all cases there was no reluctance to bear weight on the affected ankle. When an ulcer was present all the load was borne on it, the remainder of the foot being slightly elevated and the digits tending to be in a clasped position. On post-mortem examination there was no evidence of atrophy or other abnormalities of the muscles of the leg. All the above observations were made only on male STR/ORT mice. The ankles of the female STR/ORT and of both sexes of the CBA/ORT strain were normal. B. Spalteholz preparations. A normal ankle and foot are illustrated in fig. 2. The early deformity in the male STR/ORT mice was seen as a slight elevation of the calcaneum (fig. 3). The astragalus (talus) retained its position relative to the calcaneum which resulted in a forward rotation of its articulation with the distal end of the tibia. Even at an early stage there was the formation of small peri-articular calcifications seen as discrete, ectopic Alizarin Red S staining tissue. In its severest form of dislocation the calcaneum came to lie along the distal end of the tibia (fig. 4). Calcified and ossified heterotopic tissue largely obscured the navicular and tarsal bones though they generally appeared to remain in their normal positions. In deformed ankles there was a marked enlargement of the single, or sometimes double, spindle-shaped ectopic calcification which is always present in the Achilles tendons of these mice when they are over the age of 7 mth (fig. 4).
Radiological appearances The radiographs of two normal ankles are illustrated in fig. 5. In the early deformity the elevation of the calcaneum was clearly seen (fig. 6). In most cases there was a forward rotation of the astragalus (talus) relative to the tibia but its position relative to the calcaneum remained the same. The dislocation of the calcaneum in many individuals was such that it had become superimposed on the distal end of the tibia (fig. 7). At this stage there were sometimes varying degrees of disruption to the navicular and tarsal bones, though usually they retained their normal locations relative to the other bones of the foot. However, their articulations with the astragalus and calcaneum were severely dislocated. Invariably, widespread calcification was observed around the whole ankle once the calcaneum was completely displaced (fig. 7). A spindle-shaped calcification within the Achilles tendon was a characteristic of STR/ORT mice of both sexes by 8 mth of age but their appearance in the majority of CBA/ORT mice was delayed until 19 mth. In the deformed ankles of male STR/ORT mice these tendinous calcifications were noticeably enlarged. In a small minority of ankles heavy peri-articular and Achilles tendon calcifications and ossifications were present around otherwise normal, non-disrupted joints. At the end of the 14 mth of the serial survey five of the original 30 male
MOUSE ANKLE DEFORMITY
191
STR/ORT mice had developed severe ankle deformities. It had taken 6-8 mth for them to develop from the first indication of a subluxating calcaneum. Radiographic incidence of the deformity With the exception of one female STR/ORT mouse the deformity was found only in the males of that strain. A total of 352 male STRjORT ankles were examined radiographically; with a few exceptions this was carried out post mortem. As the deformity was slow in developing it could not be classified according to its grade of severity, therefore each ankle was assessed only for the presence or absence of deformation. The overall incidence after its first appearance at 4 mth of age was 26.7 per cent. of all ankles of the males, 42.1 per cent. of the mice being affected in at least one ankle. The variation in the incidence of the deformity with age is shown in the table. There was little TABLE Age range (months) 0-3 4-6 7-9 1ii2 13-15 16-18 19+
*
No. of ankles* 81 33 94
68 38 10 28
Incidence of deformed ankles (per cent.) RT 0 25.0 47.9
LT 0 23.5
26.3 40.0 14.3
21 -2 21.1 20.0 26.7
i7.i
37.0
Mice with Mice with both deformed ankle(s) ankles deformed (per cent.) (per cent.) 0 35.0
53.0 .. .
27.0 36.8 60.0 41.0
0 13.5 _35.0 _10.1 9.0 0
0 For technical reasons both ankles of each mouse were not necessarily seen radiographically.
difference between the incidence of the deformity in the right leg and the left leg over all the age groups, though there were marked differences at specific ages. The incidence of mice, with at least one deformed ankle, varied inconsistently through the various age groups. There was an increased tendency with age for only one ankle to be affected. However, these data do not necessarily represent the age of onset of the deformity but rather the condition of the ankles post mortem. Relationship to osteoarthrosis of the knee (a) The knee joints of the same male STR/ORT mice had previously been assessed for radiological signs of osteoarthrosis (Walton, 1977a). In order to establish whether there was a correlation between degenerative joint disease of the knee and a deformity of the ankle of the same leg, a statistical analysis was carried out. A 2 x 2 contingency table was prepared from the data, recording the number of legs with or without osteoarthrosis, and in each case whether there was the presence or absence of a calcaneal elevation. A X 2 test was applied and the results indicated no correlation between the two features (P= 10.0-5.0). (b) A certain number of individual mice had a deformed ankle in a leg
192
MARK WALTON
with a normal knee; the contralateral leg had an arthrosic knee but normal ankle. This suggested that a degenerate knee might cause the animal to put greater weight on to its other leg, thereby initiating an ankle deformity. However, of 35 mice with an ankle deformity in one leg, there were only 20 who had osteoarthrosis in the contralateral knee.
DISCUSSION The disruption of the joints of the ankle in STR/ORT mice has similarities to two conditions found in man, congenital vertical talus and talipes dorsalis. However, both of these conditions are present in humans from birth, which is in contrast to the slow development of the vertical calcaneum in STR/ORT mice above the age of 3 mth. The human arthropathies also give rise to an abnormal gait whereas the affected mice appear to have normal mobility except in the very few instances of large soft tissue swellings. In addition, thick periarticular heterotopic calcification and ossification do not develop in the human deformities. Sokoloff (1971, personal communication) has observed various sores and xanthoma-like bumps on the feet of members of the STR/IN strain, of which the STR/ORT is a substrain. However, he had not seen the deformity described in the present study. The presence of the arthropathy only in the male mice eliminates environmental factors from the possible aetiology. Both sexes of STR/ORT and CBA/ORT strains were treated identically. They were housed in plastic cages with solid floors covered with wood shavings. All the mice were fed a comprehensive breeding diet of FFG(M). There were no obvious behavioural differences between the male and the female STR/ORT mice though as a strain they were far less active than the CBA/ORT mice who were often seen hanging upside down from the wire cage tops. The continued weight-bearing on the deformed ankles, particularly those with soft tissue swelling, suggested an absence of sensitivity to pain. The response to pin-pricking on the sole of the foot and between the digits gave no consistently reproducible results with any of the mice. In humans the neuropathic (Charcot) joint develops due to the absence of the protection afforded by the sensation of pain. This type of joint exhibits the characteristics of a mechanically abused joint in that the articulating surfaces rapidly degenerate, dislocations or fractures of bone can occur, and soft tissue inflammation is common, sometimes with perforating ulcers (Turney, 1910; Soto-Hall and Haldeman, 1940; Murray, 1957; Murray and Jacobson, 1971). One male STR/ORT mouse, with both hind legs paraplegic, though only one deformed ankle, was found to have an extensive spinal neuroma. However, a histological survey of 23 male STR/ORT mice, both arthrosic and pre-arthrosic, failed to reveal the development of any spinal lesions. In addition the relatively slow pathogenesis of the mouse arthropathy (i.e., 6-8 mth in an average lifespan of 13 mth) was in complete contrast to the rapid changes occurring in human neuropathic joints.
WALTON
PLATECXV
MOUSEANKLE
FIG. 1.-Early
FIG.2.-A
DEFORMITY
FIG.1 .
FIG.2a.
FIG.2b.
FIG.3.
ankle deformity in a fresh, skinned specimen. Note how the heel is angulated to, rather than a continuation of, the plane of the foot. x 4.
normal ankle ( a ) medial and (b) lateral views. Spalteholz preparation, perfused with India ink/gelatin and stained with Alizarin Red S. x 6.
FIG.3.-Medial view of an early deformity. The posterior end of the calcaneum has become slightly elevated. Small ectopic calcifications have formed, especially around the astragalus (talus). The calcified mass within the Achilles tendon is enlarged. Spalteholz preparation stained with Alizarin Red S. x 6.
PLATECXVI
WALTON
MOUSEANKLE DEFORMITY
Fro. 4a.
FlG. 4b.
FIG.4.--A severely deformed ankle (a) medial and (b) lateral views. The calcaneum lies along the distal end of the tibia. There is heavy peri-articular calcification and the calcified tissue within the Achilles tendon is enlarged. Spalteholz preparation stained with Alizarin Red S. x 6.
FIG.5.--Radiograph of the normal ankles of an 8-mth-old male STR/ORT mouse. X 4.
FIG. 6.-Radiograph of an ankle showing early elevation of the calcaneum. x 6 .
FIG.7.-Radiograph of an ankle with a severe lesion. The calcaneum has dislocated and this has led to disruption of the joints of the ankle. Considerable amounts of mineralised heterotopic tissue are present. x 6 .
MOUSE ANKLE DEFORMITY
193
The absence of gross abnormalities in the gastrocnemius muscle suggests that haemangioma is not the cause of the constriction of the calf muscle as can occur in man (Sutherland, 1975). Muscular or neuromuscular imbalance could lead to the elevation of the calcaneum in STR/ORT mice. One form of clubfoot in man, talipes equinus, is characterised by an equinus deformity (dropped foot). The possibility remains that male STR/ORT mice may be congenitally susceptible to a clubfoot type of deformity. If this is so, the weight of the animal, borne through the normally flexed ankle joint, may prevent the whole foot from attaining an equinus position. This would cause considerable mechanical stresses: (a) In the Achilles tendon and its attachment to the calcaneum. This would explain the much earlier development of Achilles tendon calcification in STR/ ORT mice compared with CBA/ORT mice. A similar situation exists in STRjORT knee joints where soft tissue calcification and ossification occur due to abnormal stresses brought about by patella subluxation (Walton, 1977a and b). (b) Between the calcaneum, astragalus and navicular bones. It is these same joints that are disarticulated during the deformity. In addition it is around these joints that ectopic calcification first appears, and this may indicate increased mechanical stresses in the surrounding soft tissues. The added mechanical advantage about the ankle afforded by the relatively long calcaneum may make the bone more vulnerable to subluxation when the mechanical forces through the Achilles tendon are excessively high. SUMMARY
A spontaneous subluxation and subsequent dislocation of the bones of the ankle has been described in the males of an inbred strain of mouse (STR/ORT). It consisted of a gradual elevation of the calcaneum which eventually came to lie along the distal end of the tibia after 6-8 mth. The astragalus rotated forward. Articulations with the navicular and tarsal bones were severely disrupted with the accompanying development of peri-articular calcifications and ossifications. With one exception the arthropathy only occurred in male mice. Of the male members of the colony over the age of 3 mth, 26.7 per cent. had at least one ankle affected. Possible aetiological factors are discussed. This work was generously supported by the Wellcome Trustees through Dr Audrey U. Smith. REFERENCES MURRAY, R. 0. 1957. Congenital indifference to pain with special reference to skeletal changes. Brit.J . Radiol., 30, 2. MURRAY, R. O., AND JACOBSON, H. G. 1971. The radiology of skeletal disorders. Exercises in diagnosis. Churchill Livingstone, Edinburgh, p. 232. SOTO-HALL, R., and HALDEMAN, K. 0. 1940. The diagnosis of neuropathic disease (Charcot joint): An analysis of forty cases. J. Amer. Med. Ass., 114, 2076.
194
MARK WALTON
SUTHERLAND, A. D. 1975. Equinus deformity due to haemangioma of calf muscle. J. Bone Joint Surg., 57B, 104. TURNEY, H. C. 1910. Neurotrophic affections of bones and joints. In System of medicine, edited by C. Allbutt and H. D. Rolleston, Macmillan, New York. WALTON, M. 1977a. Studies of degenerative joint disease in the mouse knee. I. Radiological and morphological observations. J. Puth., 123, 97. WALTON,M. 19573. Studies of degenerative joint disease in the mouse knee. 11. Histological observations. J. Path., 123, 109. WALTON,M. 1977c. Studies of degenerative joint disease in the mouse knee. 111. Scanning electron microscopy. J. Path., 123, 211.
PLATESCXV
AND
CXVI
THEknee joints of STR/ORT mice are prone to develop degenerative joint disease (osteoarthrosis) especially in the males (Walton, 1977a, b and c). During examination of the hind legs of these mice, some were observed to have swollen ankles or an abnormal angulation between the plane of the foot and the calf. An investigation into this ankle deformity is reported here. MATERIALS AND METHODS A visual inspection was made of the ankles of both male and female STRjORT mice in a colony of 400-500 individuals. This was repeated on a smaller colony of non-arthrosis prone CBA/ORT mice (Walton, 1977a and b). Normally the calcaneum lies with its long axis in the same plane as the sole of the foot and forms an acute angle to the long axis of the tibia. Ankles which deviated from this normal form or which had soft tissue swelling were examined radiographically. For this a Picker X-ray unit was used with a 1.0 mm aluminium filter and set at 25 kV and 30 mA for an exposure of 3 s. Lateral views were taken of the ankles with the animals under halothane/NzO anaesthesia. For the protection of the animal the remainder of its body was covered by a lead shield. Having recognised a skeletal abnormality in most of these mice a review was carried out of all the post-mortem radiographs taken of STR/ORT and CBA/ORT mice during the course of a previous study (Walton, 1977a). These had been produced using a Raymax 50 X-ray unit which has a 1.5 mm focal point and a 2.0 mm beryllium filter. Exposure had been for 40 s at 30 kV and 6 mA using Kodak Industrex M film. In addition, Spalteholz preparations stained with Alizarin Red S, also produced during the previous study, were examined. A serial survey was made of 30 male STR/ORT newborn mice. Every 2 mth, over a period of 14 mth, radiographs were taken of lateral views of their ankles with the mice under anaesthesia and using the Picker equipment.
RESULTS Gross appearances A. Living animals. In the mouse the calcaneum is a particularly long bone which extends the plane of the foot and forms a definite angulation with the Achilles tendon. The earliest gross indication of a deformity was a slight elevation of the posterior end of the heel, such that it no longer formed a continuation of the plane of the foot (fig. 1). This angulation could increase up to 45" after which the heel merely appeared abnormally rounded. Soft Received 9 Sept. 1917; accepted 16 Sept. 1911.
* Present address : Department of Orthopaedic Surgery, University of Otago Medical School,
PO Box 913, Dunedin, New Zealand. 3. PATH.-VOL.
124 (1978)
189
190
MARK WALTON
tissue changes did not necessarily accompany the deformity even in its extreme form. Occasionally, when soft tissue swelling had developed, large open or healing ulcers covered most of the weight-bearing surface of the heel. In almost all cases there was no reluctance to bear weight on the affected ankle. When an ulcer was present all the load was borne on it, the remainder of the foot being slightly elevated and the digits tending to be in a clasped position. On post-mortem examination there was no evidence of atrophy or other abnormalities of the muscles of the leg. All the above observations were made only on male STR/ORT mice. The ankles of the female STR/ORT and of both sexes of the CBA/ORT strain were normal. B. Spalteholz preparations. A normal ankle and foot are illustrated in fig. 2. The early deformity in the male STR/ORT mice was seen as a slight elevation of the calcaneum (fig. 3). The astragalus (talus) retained its position relative to the calcaneum which resulted in a forward rotation of its articulation with the distal end of the tibia. Even at an early stage there was the formation of small peri-articular calcifications seen as discrete, ectopic Alizarin Red S staining tissue. In its severest form of dislocation the calcaneum came to lie along the distal end of the tibia (fig. 4). Calcified and ossified heterotopic tissue largely obscured the navicular and tarsal bones though they generally appeared to remain in their normal positions. In deformed ankles there was a marked enlargement of the single, or sometimes double, spindle-shaped ectopic calcification which is always present in the Achilles tendons of these mice when they are over the age of 7 mth (fig. 4).
Radiological appearances The radiographs of two normal ankles are illustrated in fig. 5. In the early deformity the elevation of the calcaneum was clearly seen (fig. 6). In most cases there was a forward rotation of the astragalus (talus) relative to the tibia but its position relative to the calcaneum remained the same. The dislocation of the calcaneum in many individuals was such that it had become superimposed on the distal end of the tibia (fig. 7). At this stage there were sometimes varying degrees of disruption to the navicular and tarsal bones, though usually they retained their normal locations relative to the other bones of the foot. However, their articulations with the astragalus and calcaneum were severely dislocated. Invariably, widespread calcification was observed around the whole ankle once the calcaneum was completely displaced (fig. 7). A spindle-shaped calcification within the Achilles tendon was a characteristic of STR/ORT mice of both sexes by 8 mth of age but their appearance in the majority of CBA/ORT mice was delayed until 19 mth. In the deformed ankles of male STR/ORT mice these tendinous calcifications were noticeably enlarged. In a small minority of ankles heavy peri-articular and Achilles tendon calcifications and ossifications were present around otherwise normal, non-disrupted joints. At the end of the 14 mth of the serial survey five of the original 30 male
MOUSE ANKLE DEFORMITY
191
STR/ORT mice had developed severe ankle deformities. It had taken 6-8 mth for them to develop from the first indication of a subluxating calcaneum. Radiographic incidence of the deformity With the exception of one female STR/ORT mouse the deformity was found only in the males of that strain. A total of 352 male STRjORT ankles were examined radiographically; with a few exceptions this was carried out post mortem. As the deformity was slow in developing it could not be classified according to its grade of severity, therefore each ankle was assessed only for the presence or absence of deformation. The overall incidence after its first appearance at 4 mth of age was 26.7 per cent. of all ankles of the males, 42.1 per cent. of the mice being affected in at least one ankle. The variation in the incidence of the deformity with age is shown in the table. There was little TABLE Age range (months) 0-3 4-6 7-9 1ii2 13-15 16-18 19+
*
No. of ankles* 81 33 94
68 38 10 28
Incidence of deformed ankles (per cent.) RT 0 25.0 47.9
LT 0 23.5
26.3 40.0 14.3
21 -2 21.1 20.0 26.7
i7.i
37.0
Mice with Mice with both deformed ankle(s) ankles deformed (per cent.) (per cent.) 0 35.0
53.0 .. .
27.0 36.8 60.0 41.0
0 13.5 _35.0 _10.1 9.0 0
0 For technical reasons both ankles of each mouse were not necessarily seen radiographically.
difference between the incidence of the deformity in the right leg and the left leg over all the age groups, though there were marked differences at specific ages. The incidence of mice, with at least one deformed ankle, varied inconsistently through the various age groups. There was an increased tendency with age for only one ankle to be affected. However, these data do not necessarily represent the age of onset of the deformity but rather the condition of the ankles post mortem. Relationship to osteoarthrosis of the knee (a) The knee joints of the same male STR/ORT mice had previously been assessed for radiological signs of osteoarthrosis (Walton, 1977a). In order to establish whether there was a correlation between degenerative joint disease of the knee and a deformity of the ankle of the same leg, a statistical analysis was carried out. A 2 x 2 contingency table was prepared from the data, recording the number of legs with or without osteoarthrosis, and in each case whether there was the presence or absence of a calcaneal elevation. A X 2 test was applied and the results indicated no correlation between the two features (P= 10.0-5.0). (b) A certain number of individual mice had a deformed ankle in a leg
192
MARK WALTON
with a normal knee; the contralateral leg had an arthrosic knee but normal ankle. This suggested that a degenerate knee might cause the animal to put greater weight on to its other leg, thereby initiating an ankle deformity. However, of 35 mice with an ankle deformity in one leg, there were only 20 who had osteoarthrosis in the contralateral knee.
DISCUSSION The disruption of the joints of the ankle in STR/ORT mice has similarities to two conditions found in man, congenital vertical talus and talipes dorsalis. However, both of these conditions are present in humans from birth, which is in contrast to the slow development of the vertical calcaneum in STR/ORT mice above the age of 3 mth. The human arthropathies also give rise to an abnormal gait whereas the affected mice appear to have normal mobility except in the very few instances of large soft tissue swellings. In addition, thick periarticular heterotopic calcification and ossification do not develop in the human deformities. Sokoloff (1971, personal communication) has observed various sores and xanthoma-like bumps on the feet of members of the STR/IN strain, of which the STR/ORT is a substrain. However, he had not seen the deformity described in the present study. The presence of the arthropathy only in the male mice eliminates environmental factors from the possible aetiology. Both sexes of STR/ORT and CBA/ORT strains were treated identically. They were housed in plastic cages with solid floors covered with wood shavings. All the mice were fed a comprehensive breeding diet of FFG(M). There were no obvious behavioural differences between the male and the female STR/ORT mice though as a strain they were far less active than the CBA/ORT mice who were often seen hanging upside down from the wire cage tops. The continued weight-bearing on the deformed ankles, particularly those with soft tissue swelling, suggested an absence of sensitivity to pain. The response to pin-pricking on the sole of the foot and between the digits gave no consistently reproducible results with any of the mice. In humans the neuropathic (Charcot) joint develops due to the absence of the protection afforded by the sensation of pain. This type of joint exhibits the characteristics of a mechanically abused joint in that the articulating surfaces rapidly degenerate, dislocations or fractures of bone can occur, and soft tissue inflammation is common, sometimes with perforating ulcers (Turney, 1910; Soto-Hall and Haldeman, 1940; Murray, 1957; Murray and Jacobson, 1971). One male STR/ORT mouse, with both hind legs paraplegic, though only one deformed ankle, was found to have an extensive spinal neuroma. However, a histological survey of 23 male STR/ORT mice, both arthrosic and pre-arthrosic, failed to reveal the development of any spinal lesions. In addition the relatively slow pathogenesis of the mouse arthropathy (i.e., 6-8 mth in an average lifespan of 13 mth) was in complete contrast to the rapid changes occurring in human neuropathic joints.
WALTON
PLATECXV
MOUSEANKLE
FIG. 1.-Early
FIG.2.-A
DEFORMITY
FIG.1 .
FIG.2a.
FIG.2b.
FIG.3.
ankle deformity in a fresh, skinned specimen. Note how the heel is angulated to, rather than a continuation of, the plane of the foot. x 4.
normal ankle ( a ) medial and (b) lateral views. Spalteholz preparation, perfused with India ink/gelatin and stained with Alizarin Red S. x 6.
FIG.3.-Medial view of an early deformity. The posterior end of the calcaneum has become slightly elevated. Small ectopic calcifications have formed, especially around the astragalus (talus). The calcified mass within the Achilles tendon is enlarged. Spalteholz preparation stained with Alizarin Red S. x 6.
PLATECXVI
WALTON
MOUSEANKLE DEFORMITY
Fro. 4a.
FlG. 4b.
FIG.4.--A severely deformed ankle (a) medial and (b) lateral views. The calcaneum lies along the distal end of the tibia. There is heavy peri-articular calcification and the calcified tissue within the Achilles tendon is enlarged. Spalteholz preparation stained with Alizarin Red S. x 6.
FIG.5.--Radiograph of the normal ankles of an 8-mth-old male STR/ORT mouse. X 4.
FIG. 6.-Radiograph of an ankle showing early elevation of the calcaneum. x 6 .
FIG.7.-Radiograph of an ankle with a severe lesion. The calcaneum has dislocated and this has led to disruption of the joints of the ankle. Considerable amounts of mineralised heterotopic tissue are present. x 6 .
MOUSE ANKLE DEFORMITY
193
The absence of gross abnormalities in the gastrocnemius muscle suggests that haemangioma is not the cause of the constriction of the calf muscle as can occur in man (Sutherland, 1975). Muscular or neuromuscular imbalance could lead to the elevation of the calcaneum in STR/ORT mice. One form of clubfoot in man, talipes equinus, is characterised by an equinus deformity (dropped foot). The possibility remains that male STR/ORT mice may be congenitally susceptible to a clubfoot type of deformity. If this is so, the weight of the animal, borne through the normally flexed ankle joint, may prevent the whole foot from attaining an equinus position. This would cause considerable mechanical stresses: (a) In the Achilles tendon and its attachment to the calcaneum. This would explain the much earlier development of Achilles tendon calcification in STR/ ORT mice compared with CBA/ORT mice. A similar situation exists in STRjORT knee joints where soft tissue calcification and ossification occur due to abnormal stresses brought about by patella subluxation (Walton, 1977a and b). (b) Between the calcaneum, astragalus and navicular bones. It is these same joints that are disarticulated during the deformity. In addition it is around these joints that ectopic calcification first appears, and this may indicate increased mechanical stresses in the surrounding soft tissues. The added mechanical advantage about the ankle afforded by the relatively long calcaneum may make the bone more vulnerable to subluxation when the mechanical forces through the Achilles tendon are excessively high. SUMMARY
A spontaneous subluxation and subsequent dislocation of the bones of the ankle has been described in the males of an inbred strain of mouse (STR/ORT). It consisted of a gradual elevation of the calcaneum which eventually came to lie along the distal end of the tibia after 6-8 mth. The astragalus rotated forward. Articulations with the navicular and tarsal bones were severely disrupted with the accompanying development of peri-articular calcifications and ossifications. With one exception the arthropathy only occurred in male mice. Of the male members of the colony over the age of 3 mth, 26.7 per cent. had at least one ankle affected. Possible aetiological factors are discussed. This work was generously supported by the Wellcome Trustees through Dr Audrey U. Smith. REFERENCES MURRAY, R. 0. 1957. Congenital indifference to pain with special reference to skeletal changes. Brit.J . Radiol., 30, 2. MURRAY, R. O., AND JACOBSON, H. G. 1971. The radiology of skeletal disorders. Exercises in diagnosis. Churchill Livingstone, Edinburgh, p. 232. SOTO-HALL, R., and HALDEMAN, K. 0. 1940. The diagnosis of neuropathic disease (Charcot joint): An analysis of forty cases. J. Amer. Med. Ass., 114, 2076.
194
MARK WALTON
SUTHERLAND, A. D. 1975. Equinus deformity due to haemangioma of calf muscle. J. Bone Joint Surg., 57B, 104. TURNEY, H. C. 1910. Neurotrophic affections of bones and joints. In System of medicine, edited by C. Allbutt and H. D. Rolleston, Macmillan, New York. WALTON, M. 1977a. Studies of degenerative joint disease in the mouse knee. I. Radiological and morphological observations. J. Puth., 123, 97. WALTON,M. 19573. Studies of degenerative joint disease in the mouse knee. 11. Histological observations. J. Path., 123, 109. WALTON,M. 1977c. Studies of degenerative joint disease in the mouse knee. 111. Scanning electron microscopy. J. Path., 123, 211.
