Developmental Neuroscience

Original Papers

Experimental Maternal Phenylketonuria: An Examination of Two Animal Models

Loo Y.H. · Rabe A. · Potempska A. · Wang P. · Fersko R. · Wisniewski H.M.

Author affiliations

New York State Institute for Basic Research in Developmental Disabilities, Staten Island, N.Y., USA

Related Articles for ""

Dev Neurosci 1983–84;6:227–234

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Article / Publication Details

First-Page Preview
Abstract of Original Papers

Received: March 29, 1984
Accepted: September 03, 1984
Published online: June 29, 2009
Issue release date: 1984

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

Abstract

Two satisfactory rat models of maternal phenylketonuria (PKU) have been developed. Continuous subcutaneous infusion into pregnant rats from the 9th–20th day of gestation of either (1) phenylacetate (PA), to elevate plasma levels of unconjugated PA to 0.25–0.60 /μmol/ml, or (2) a nontoxic dose (0.2 μmol/g/day) of p-chlorophenylalanine (pClPhe) with L-phenylalanine (Phe), to elevate plasma Phe levels at least 10-fold (1.7–2.3 μmol/ml) and unconjugated PA to at least 0.2 μmol/ml, produced the syndrome of untreated maternal PKU: spontaneous abortion, mortality rate greater than normal among the newborn, retarded growth of fetal body and brain, and a learning deficit among the progeny. From the plasma of rats infused with only pClPhe, a metabolite was isolated and identified as p-chlorophenylacetic acid. This compound, at a concentration greater than 0.15 μmol/ml plasma was found to retard fetal body and brain growth. In the pregnant rat, plasma levels of unconjugated PA, in the range observed in some PKU individuals on a normal diet, effectively induced a simulation of maternal PKU. The results of this investigation support our contention that PA, which is produced in excessive amounts in clinical PKU, is the primary cause of the brain dysfunction.

© 1983 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Original Papers

Received: March 29, 1984
Accepted: September 03, 1984
Published online: June 29, 2009
Issue release date: 1984

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE


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