Phenylalanine Metabolism in a Dilute-Lethal Strain of Mice

Some observations on the blood levels of phenylalanine in dilute mice and a comparison between human phenylketonuria and the disease of mice homozygous for the dilute lethal gene

“…The blood levels of phenylalanine in dilute lethal mice in the present experiments were found to be the same as the other genotypes of the same age, thus agreeing with the findings of Woolf (1963), Zannoni et al (1966) and Mauer & Sideman (1967). The exceptions occurred in the two mice which were considered to be dying, Their greatly elevated plasma phenylalanine levels suggest that a breakdown in the activity of the relevant enzyme system in the liver precedes death, allowing phenylalanine to accumulate.…”

“…However, the initial findings on phenylalanine metabolism could not be substantiated. Woolf (1963), Zannoni et al (1966) and Mauer & Sideman (1967) could find no increase in blood phenylalanine, and no abnormality in the liver phenylalanine hydroxylase activity. Finally, Zannoni & Moraru (1970) did discover a quantitative alteration in the phenylalanine hydroxylase system with a concomitant rise in blood phenylalanine when the animal was overloaded by dietary supplementation of phenylalanine.…”

The Coat Colors of Mice

“…Accordingly they suggested "that reduced enzyme activities lead to elevation in serum phenylalanine level which may in turn be responsible for those behavioral abnormalities that are related to myelin degeneration in the brain." On the other hand, Mauer and Sideman (1967) found that dl/d l mice displayed no difference from their normal littermates in levels of serum phenylalanine. Assays of liver phenylalanine hydroxylase activity, based on radioactive tracer methods, also failed to reveal any defect in this aspect of phenylalanine metabolism.…”

“…2 Thus the d 1 (for dilute-lethal) mutation 3 -a mutation recessive to both D and d-is phenotypically indistinguishable from did but, unlike d, produces a severe neuromuscular disorder characterized by convulsions and opisthotonus (arching upward of the head and tail). Myelin degeneration occurs in the CNS of d 1 homozygotes (Kelton and Rauch, 1962) and they usually die at about 3 weeks of age (Searle, 1952).4 Although it has been reported that phenylalanine metabolism is seriously disturbed in these mice (Coleman, 1960;Rauch and Yost, 1963) this remains to be confirmed (Zannoni et at, 1966;Mauer and Sideman, 1967).5…”