Micro-magnetic resonance imaging and embryological analysis of wild-type and pma mutant mice with clubfoot

Suzanne Duce, Londale Madrigal, Katy Schmidt, Craig Cunningham, Guoqing Liu, Simon Barker, Gordon Tennant, Cheryll Tickle, Sandy Chudek, Zosia Miedzybrodzka

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    Abstract

    Gross similarities between the external appearance of the hind limbs of the peroneal muscle atrophy (pma) mouse mutant and congenital talipes equinovarus (CTEV), a human disorder historically referred to as 'clubfoot', suggested that this mutant could be a useful model. We used micro-magnetic resonance imaging to visualize the detailed anatomy of the hind limb defect in mutant pma mice and performed 3D comparisons between mutant and wild-type hind limbs. We found that the pma foot demonstrates supination (i.e. adduction and inversion of the mid foot and fore foot together with plantar flexion of the ankle and toes) and that the tibiale and distal tarsals display 3D abnormalities in positioning. The size and shape of the tibia, fibula, tarsal and metatarsal bones are similar to the wild-type. Hypoplasia of the muscles in the antero-lateral (peroneal) compartment was also demonstrated. The resemblance of these features to those seen in CTEV suggests that the pma mouse is a possibly useful model for the human condition. To understand how the observed deformities in the pma mouse hind foot arise during embryonic development, we followed the process of foot rotation in both wild-type and pma mutant mice. Rotation of the hind foot in mouse embryos of wild-type strains (CD-1 and C57/Black) occurs from embryonic day 14.5 onwards with rotation in C57/Black taking longer. In embryos from both strains, rotation of the right hind foot more commonly precedes rotation of the left. In pma mutants, the initiation of rotation is often delayed and rotation is slower and does not reach completion. If the usefulness of the pma mutant as a model is confirmed, then these findings on pma mouse embryos, when extrapolated to humans, would support a long-standing hypothesis that CTEV is due to the failure of completion of the normal process of rotation and angulation, historically known as the 'arrested development hypothesis'.
    Original languageEnglish
    Pages (from-to)108-120
    Number of pages13
    JournalJournal of Anatomy
    Volume216
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Fingerprint

    Clubfoot
    muscular atrophy
    Muscular Atrophy
    magnetic resonance imaging
    muscle
    Magnetic Resonance Imaging
    Foot
    mutants
    mice
    limbs (animal)
    embryo (animal)
    limb
    Embryonic Structures
    Extremities
    embryo
    Tarsal Bones
    fibula
    Supination
    mutant
    analysis

    Cite this

    Duce, Suzanne ; Madrigal, Londale ; Schmidt, Katy ; Cunningham, Craig ; Liu, Guoqing ; Barker, Simon ; Tennant, Gordon ; Tickle, Cheryll ; Chudek, Sandy ; Miedzybrodzka, Zosia. / Micro-magnetic resonance imaging and embryological analysis of wild-type and pma mutant mice with clubfoot. In: Journal of Anatomy. 2010 ; Vol. 216, No. 1. pp. 108-120.
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    abstract = "Gross similarities between the external appearance of the hind limbs of the peroneal muscle atrophy (pma) mouse mutant and congenital talipes equinovarus (CTEV), a human disorder historically referred to as 'clubfoot', suggested that this mutant could be a useful model. We used micro-magnetic resonance imaging to visualize the detailed anatomy of the hind limb defect in mutant pma mice and performed 3D comparisons between mutant and wild-type hind limbs. We found that the pma foot demonstrates supination (i.e. adduction and inversion of the mid foot and fore foot together with plantar flexion of the ankle and toes) and that the tibiale and distal tarsals display 3D abnormalities in positioning. The size and shape of the tibia, fibula, tarsal and metatarsal bones are similar to the wild-type. Hypoplasia of the muscles in the antero-lateral (peroneal) compartment was also demonstrated. The resemblance of these features to those seen in CTEV suggests that the pma mouse is a possibly useful model for the human condition. To understand how the observed deformities in the pma mouse hind foot arise during embryonic development, we followed the process of foot rotation in both wild-type and pma mutant mice. Rotation of the hind foot in mouse embryos of wild-type strains (CD-1 and C57/Black) occurs from embryonic day 14.5 onwards with rotation in C57/Black taking longer. In embryos from both strains, rotation of the right hind foot more commonly precedes rotation of the left. In pma mutants, the initiation of rotation is often delayed and rotation is slower and does not reach completion. If the usefulness of the pma mutant as a model is confirmed, then these findings on pma mouse embryos, when extrapolated to humans, would support a long-standing hypothesis that CTEV is due to the failure of completion of the normal process of rotation and angulation, historically known as the 'arrested development hypothesis'.",
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    Duce, S, Madrigal, L, Schmidt, K, Cunningham, C, Liu, G, Barker, S, Tennant, G, Tickle, C, Chudek, S & Miedzybrodzka, Z 2010, 'Micro-magnetic resonance imaging and embryological analysis of wild-type and pma mutant mice with clubfoot', Journal of Anatomy, vol. 216, no. 1, pp. 108-120. https://doi.org/10.1111/j.1469-7580.2009.01163.x

    Micro-magnetic resonance imaging and embryological analysis of wild-type and pma mutant mice with clubfoot. / Duce, Suzanne; Madrigal, Londale; Schmidt, Katy; Cunningham, Craig; Liu, Guoqing; Barker, Simon; Tennant, Gordon; Tickle, Cheryll; Chudek, Sandy; Miedzybrodzka, Zosia.

    In: Journal of Anatomy, Vol. 216, No. 1, 01.2010, p. 108-120.

    Research output: Contribution to journalArticle

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    AU - Duce, Suzanne

    AU - Madrigal, Londale

    AU - Schmidt, Katy

    AU - Cunningham, Craig

    AU - Liu, Guoqing

    AU - Barker, Simon

    AU - Tennant, Gordon

    AU - Tickle, Cheryll

    AU - Chudek, Sandy

    AU - Miedzybrodzka, Zosia

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