신생(新生)쥐의 생후(生後) 2주간(週間)에 있어서 Phenylketonuria 적(的) 조건(條件)의 실험적(實驗的) 유도(誘導)

Induction of an Experimental PKU-Like Condition in Infant Rats During the First Two Weeks After Birth

Phenylketonuria (PKU)의 여러가지 특성(特性)을 연구(硏究)하기 위(爲)하며 신생(新生)쥐에 실험적(實驗的)으로 PKU를 유도(誘導)시키는 방법(方法)을 실험(實驗)하였다. 신생(新生)쥐에 생후(生後) 2일부터 5일까지는 체중(體重) kg당 400mg의 Phenylalanine을, 6일부터 14일까지는 500mg의 Phenylalanine을 오전(午前) 6시(時)부터 매(每) 6시간(時間)마다 위(胃)에서 주입(注入)시켰으며 생후(生後) 3일부터 14일까지는 체중(體重) kg당 0.00625~0.0125mg의 amethopterin을, 5일부터 14일까지는 체중(體重) kg 당 50mg의 P-chlorophenylalanine을 오전(午前) 및 오후(午後) 9시(時) 매일(每日) 2회 투여(投與)한후 Phenylalanine/tyrosine (P/T), 와 여러가지 외관적(外觀的)인 증상(症狀)을 조사(調査)한 결과(結果) Phenylalanine, amethopterin및 P-chlorophenylalanine을 동시(同時)에 투여(投與)한 경우는 P/T-비(比)가 정상치이상(正常値以上)으로 증가(增加)됨과 동시(同時)에 비정상적(非正常的)인 자세(姿勢), 비틀거리는 걸음걸이와 같은 PKU 증상(症狀)이 나타났으나 Phenylanine이나 저해제(沮害制) 단독투여시(單獨投與時)는 PKU 증상(症狀)이 나타나지 않았다.

The objective of this study is to induce the primary characteristics of phenylketonuria in infant rats during the first 2 weeks after birth. The critical biochemical parameter in the development of phenylketonuria is the elevation of plasma phenylalanine while tyrosine is maintained at a relatively low level. A PKU-like condition was induced in infant rats during the first 2 weeks after birth using a modification of our previously published procedure for the development of a temporary (1 to 3 days) PKU-like condition. Phenylalanine was administered by stomach intubation every 6 hours (starting at 6:00 a.m.) at a dose level of 400mg per kg body weight (after birth-day 2 thru 5) and 500mg per kg body weight (day 6 thru 14). Amethopterin was given at 0.00625 or 0.0125mg per kg body weight (day 3 thru 14) and p-chlorophenylalanine at 50 mg per kg body weight (day 5 thru 14) at 9:00 a.m. and 9:00 p.m. At the times measured (6,10 and 14 days) plasma phenylalanine/tyrosine (P/T) ratios were elevated from a normal value of the or less to values ranging from 6 to 15. During the second week after birth a staggering gait, abnormal stance and decreased social behavior were also observed. None of these PKU-like characteristics were apparent in the three control groups receiving (a) no phenylalanine or inhibitors, (b) phenylalanine alone, or (c) inhibitors alone. The establishment of these primary biochemical characteristics of phenylketonuria by stomach intubation of phenylalanine and a combination of low dose levels of enzyme inhibitors to infant rats provides an experimental system which should he valuable for extensive biochemical, histological and behavioral studies in phenylketonuria.