| Project/Area Number |
62480229
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
OKADA Shintaro Osaka University Medical School Professor, 医学部, 教授 (30028609)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIDORIKAWA Mitsuo Osaka University Medical School Lecturer, 医学部, 助手 (00200072)
INUI Koji Osaka University Medical School Lecturer, 医学部, 助手 (90175208)
|
|---|
| Project Period (FY) |
1987 – 1989
|
| Project Status |
Completed (Fiscal Year 1989)
|
| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
|
|---|
| Keywords | microinjection / inborn errors of lipid metabolism / Krabbe disease / model animal / myelination / 脱髄 / 先天性代謝病 / ガラクトセレブロシド / ガラクトセレブロシダーゼ / Krabbe病 / Twitcherマウス / 脂質代謝異常症 / 脂質代謝 |
|---|
| Research Abstract |
The pathogenesis in twitcher mouse was investigated by examining in vivo syntheses of galactosylceramide (Galcer) and galactosylsphingosine (Galsph) in a sciatic nerve culture and in vitro enzymic activities for syntheses of Galcer and Galsph in spinal cord from normal and the affected mice. For in vivo study, sciatic nerve was incubated for 24h with the medium containing (_3H)-galactose, or (_3H)-sphingosine-labeled Galcer or Galsph. In the study of (_3H)-galactose feeding, reduced synthesis of Galcer was found as early as 1 week of age and the synthesis dropped to about 15% of normal value at 4 weeks of age in the affected mice.
Increased amount of Galsph was detected in the study of 7 days feeding of galactose in the affected mouse. In the study of (_3H)-sphingosine labeled Galcer or Galsph feeding, Galsph synthesis was not found from Galcer in normal and affected mice and Galcer synthesis was found from Galsph in only normal mice, suggesting that Galcer was synthesized from sphingosine after hydrolysis of Galsph. In vitro study, the activities of UDP-galactose: ceramide galactosyltransferase and UDP-galactose: sphingosine galactosyltransferase were reduced to below 50% of control after 2 weeks of age in the affected mice. From these results, we have reached the conclusion sa follows: (1) no accumulation of Galcer was due to the decreased synthesis of Galcer, (2) Galsph was synthesized from galactose but not from deacylation of Galcer, and (3) Galsph accumulation was not-due to the increased synthesis but due to the decreased hydrolysis.
|
