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Dietary Methionine does not Reduce Penetrance in Curly Tail Mice but Causes a Phenotype-Specific Decrease in Embryonic Growth¹

Henny W. M. Van Straaten^*,2, Henk Blom, Marian C. E. Peeters^*, Anita M. J. Rousseau^*, Kathy J. Cole^,3 and Mary J. Seller

^* Department of Anatomy/Embryology, School of Medicine, University of Limburg, Maastricht, Netherlands Department of Child Health and Neurology, School of Medicine, University of Nijmegen, Nijmegen, Netherlands Division of Medical and Molecular Genetics, United Medical and Dental Schools of Guy's and St Thomas's Hospitals London SE1 9RT, UK

The mouse mutation, curly tail, has incomplete penetrance and variable expression. Approximately 60% of the mice have a curly tail (CT), from which up to 20% may have lumbosacral spina bifida. Approximately 40% are normal, with a straight tail (ST). We tested whether L-methionine, which reduces the penetrance of neural tube defects in the Axd mouse mutant, has beneficial effects in the curly tail mutant. A single injection of L-methionine (200–1600 mg/kg body wt) on d 9 of pregnancy had no effect on the embryos, whereas there was a minor increase in penetrance at the highest dose. Chronic supplementation of L-methionine via the drinking water (1554 mg·kg body wt^-1·d^-1) did not shift penetrance. However, it decreased the weight of d 13 embryos from ST dams but not of those from CT dams. This phenotype-specific difference in response was evident and most unexpected. Mice from curly tail and other inbred strains were subjected to an L-methionine loading test and serum homocysteine assay. The different strains varied in their basal serum homocysteine concentrations, and they had proportionate significant increases after L-methionine loading. In CT and ST mice, basal serum homocysteine concentrations as well as the levels after loading were similar to each other and intermediate in the range of the mice tested. We conclude that L-methionine does not reduce penetrance in the curly tail mouse and that this strain reflects no derangement in L-methionine handling.

KEY WORDS: • mice • embryo • curly tail • L-methionine • homocysteine

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with USC section 1734 solely to indicate this fact.

² To whom correspondence should be addressed.

³ Present address: Institute of Cancer Research, The Haddow Laboratory, Sutton, Surrey, UK.

Manuscript received 31 December 1994. Revision accepted 30 June 1995.