Animal model for hyperprolinaemia: deficiency of mouse proline oxidase activity.

New reports are described each year on the occurrence of human metabolic diseases due to specific enzyme deficiencies (Harris, 1970; McKusick, 1971). For the biomedical scientist interested either in the mode of genetic transmission of these biochemical traits or in the mammalian control mechanisms of gene-enzyme expression it would be desirable to be able to supplement the research on human beings with investigations on appropriate animal models. With regard to human hyperprolinaemia two variants of this metabolic disorder have been described (Efron, 1966). Shafter et al. (1962) reported a familial hyperprolinaemia associated with cerebral dysfunction and renal anomalies occurring in a family with hereditary nephropathy and deafness. A second case of familial hyperprolinaemia, reported by Efron (1965), was associated with congenital renal malformation, hereditary haematuria and mild mental retardation. The metabolic disorder in the second case was further associated with a deficiency of liver proline oxidase activity. Hyperprolinaemia caused by a deficiency of liver proline oxidase activity has been classified (Efron, 1966) as type I hyperprolinaemia (Scheme 1). Efron (1966) also described a second type of hyperprolinaemia, possibly caused by a deficiency of the enzyme Al-pyrroline-5-carboxylate dehydrogenase, although the metabolic block was not established. In type II hyperprolinaemia there was no evidence of renal disease as assessed by intravenous pyleography, blood urea N and creatinine clearance tests. Chromatograms of amino acids in the urine showed a spot with the chromatographic position and staining characteristics ofAl-pyrroline-5-carboxylate. A deficiency of the second enzyme in the degradation pathway of proline, Al-pyrroline-5-carboxylate dehydrogenase, would be expected to result in accumulation of Al-pyrroline-5-carboxylate as well