Spindle Leg Syndrome 3
Peter Marsters,
Division of Clinical Chemistry,
School of Clinical Laboratory Sciences,
University Hospital,
Queen's Medical Centre,
Nottingham, NG7 2UH.
21. 08. 99
Last update: 17 August, 2002
'I have been handed a paper entitled Developments in the study of Spindle leg syndrome, and have been requested to forward helpful suggestions. Although I am very happy to do this I must state from the start that this is not my area of expertise and my comments must therefore be generalised.
'I have not come across the ‘XLHBox 1’ gene but assume that it expresses a protein essential to limb development. As you may know all homeobox genes express developmental proteins, which may have no function in the adult organism. You say that when this gene is disrupted under laboratory conditions Spindle leg can be induced. I assume that the gene is actually ‘knocked out’ in the spawn so that the developing embryo does not receive any expressed protein from the XLHBox 1 gene.
'It is well known that some genes are much more susceptible to environmental effects than others. The reasons for this have not yet been fully elucidated. However the expressing genes must be accessible to the nuclear transcription machinery and as such are certainly on exposed locations in the chromosomes. Therefore mutations of this gene could occur during the spawn stage. Spawn is often very exposed to environmental and external influences, such as toxins in the water or high exposure to harmful ultraviolet radiation. Also in support of this is the fact that during development, genome replication occurs with high frequency and mutations commonly occur due to errors in the replicate DNA. If vitamin E does have a protective role during DNA replication, then it follows that its presence would be most beneficial during the developmental stages when crucial differentiation of pluripotent cells is occurring and replication is frequent.
'Folic acid may have a role in the ‘switching on’ of developmental genes. Thus, in the case of oviparous creatures, it seems possible that the mother donates it and vitamin E to the oocytes prior to spawning. On that basis your suggestion to treat the ‘mother’ frogs, in the period directly before spawning, with Folic acid and vitamin E would seem sound.
'It would be most interesting to test your theory, but impractical for you to do so alone since statistical evidence would require a large cohort of results. Studies of this type need to be strictly governed. Ideally they should be ‘blind’ in so much that the individuals responsible for feeding the frogs should not be aware of which frogs receive the supplement and which the placebo until after the results have been recorded. Statistical significance would need to be established and it would be necessary to repeat the experiment several times using different amounts of Folic acid and vitamin E in order to optimise dosage. However if a study of this nature is not possible I see no reason why your frogs should not be treated with Folic acid and 'Vitamin E, prior to spawning, as a prophylactic.
'It seems from your most interesting article that the similarities between Spina bifida and spindle leg do suggest that incidences of spindle leg may indeed be reduced by a similar treatment of the supplement used during human gestation. You appear to have collected your evidence scientifically and made reasonable deductions. It may be of use to you to further evaluate the roles of vitamin E and Folic acid in expectant humans, as it seems likely that these may have an application in the gravid frog and her spawn.
'I do hope that my comments may be of some use to you and I wish you every success in your endeavours.'
Peter Marsters
Read Spindle Leg 1
Read Spindle Leg 2
Read Spindle Leg 4