Mouse Genome Informatics
hm
    cl/cl
Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• many homozygotes die within 2 days after birth
• at birth, the sex ratio is significantly skewed, roughly 2 females: 3 males, suggesting that pre-natal survival of female homozygotes is reduced
• 59% of homozygotes die before 14 days of age
• many of these are lost by starvation due to inter-litter competition for milk
• 28% of homozygotes that survive the pre-weaning period die by 50 days of age
• an additional 3% die by 100 days of age
• only 9.5% survive over 100 days, with the oldest homozygote surviving to 297 days whereas its wild-type sib survived to 599 days

growth/size/body
• at birth and thereafter, homozygotes are slightly lighter in weight than wild-type littermates
• homozygotes display a reduced growth rate

limbs/digits/tail
• soft fleshy pads of tissue are noted on the weight-bearing areas of both fore- and hindlimbs
• homozygotes display flaccid digits, even in the absence of clubfoot
• digits are splayed apart or held together depending on the position and movement of the animal
• homozygotes show a significant increase in the incidence and extent of tarsal bone fusions relative to control mice
• homozygotes display congenital dorsiflexed (simple calcaneun type) bilateral clubbing of the hindfeet
• unilateral and bilateral clubbing of the forefeet is frequently observed
• homozygotes exhibit frequent unilateral and bilateral clubbing of the forefeet
• forelimbs appear abnormal even in the absence of clubfoot, as digits display the same flaccidity observed in clubbed feet
• in addition, 8 of 157 homozygotes display variable dorsiflexion and eversion of the lower forelimbs both uni- and bilaterally
• homozygotes exhibit congenital bilateral clubbing of the hindfeet
• the hindlimbs are abnormally positioned, and the skin is frequently rubbed off on the weight-bearing region of the heel
• homozygotes show a significant increase in the incidence and extent of carpal bone fusions relative to control mice
• most homozygotes loop their tails forward over their back while walking

skeleton
• homozygotes show a significant increase in the incidence and extent of tarsal bone fusions relative to control mice
• homozygotes show a significant increase in the incidence and extent of carpal bone fusions relative to control mice

muscle
• homozygotes show a marked reduction of muscular tissues in the lower limbs, such that separation of individual muscles is almost unfeasible
• however, muscles controlling palmar flexion are present, and muscles of the upper limbs appear normal

behavior/neurological
• when suspended by the tail, homozygotes are unable to grip a slender supporting object with their digits
• loss of tenacity is, to some extent, compensated by the use of pincer movements of the limbs
• homozygotes show an atypical position of the limbs and are unable to plantar flex their hindfeet
• when homozygotes are held firmly, clubbed feet can be moved manually to the normal position; when released, the feet return to their original position
• when clubbed hindfeet are forcibly plantar flexed, the skin on the dorsum of the foot is thrown up in longitudinal ridges; not observed in clubbed forefeet

reproductive system
• the fertility of both sexes is lower than normal

vision/eye
• eyes are often blocked by a viscous discharge
• eyelids are often gummed together by a viscous ocular discharge
• the area between the eyelids is often reduced
• the eyelids are occasionally denuded of hair

integument
• the eyelids are occasionally denuded of hair

Mouse Models of Human Disease
OMIM IDRef(s)
Clubfoot, Congenital, with or without Deficiency of Long Bones and/or Mirror-Image Polydactyly; CCF 119800 J:294