| A noncoding RNA modulator potentiates phenylalanine metabolism in mice. | A noncoding RNA modulator potentiates phenylalanine metabolism in mice.
Li Y, Tan Z, Zhang Y, Zhang Z, Hu Q, Liang K, Jun Y, Ye Y, Li YC, Li C, Liao L, Xu J, Xing Z, Pan Y, Chatterjee SS, Nguyen TK, Hsiao H, Egranov SD, Putluri N, Coarfa C, Hawke DH, Gunaratne PH, Tsai KL, Han L, Hung MC, Calin GA, Namour F, Guéant JL, Muntau AC, Blau N, Sutton VR, Schiff M, Feillet F, Zhang S, Lin C, Yang L., Free PMC Article | 08/21/2021 |
| Mesenchymal stem cell energy deficit and oxidative stress contribute to osteopenia in the Pah(enu2) classical PKU mouse. | Mesenchymal stem cell energy deficit and oxidative stress contribute to osteopenia in the Pah(enu2) classical PKU mouse.
Dobrowolski SF, Sudano C, Phua YL, Tourkova IL, Spridik K, Goetzman ES, Vockley J, Blair HC., Free PMC Article | 08/7/2021 |
| A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency. | A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.
Richards DY, Winn SR, Dudley S, Fedorov L, Rimann N, Thöny B, Harding CO., Free PMC Article | 07/10/2021 |
| The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase. | The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase.
Aubi O, Prestegård KS, Jung-Kc K, Shi TS, Ying M, Grindheim AK, Scherer T, Ulvik A, McCann A, Spriet E, Thöny B, Martinez A., Free PMC Article | 04/17/2021 |
| In PAH deficient MSCs, expression of Col1A1 and Rankl are suppressed by hyperphenylalaninemia consistent with reduced bone formation and bone turnover. Osteopenia is intrinsic to phenylketonuria (PKU) pathology in untreated Pah(enu2) animals and our data suggests PHE toxicity participates by inhibiting mineralization in the course of MSC bone differentiation. | A bone mineralization defect in the Pah(enu2) model of classical phenylketonuria involves compromised mesenchymal stem cell differentiation.
Dobrowolski SF, Tourkova IL, Robinson LJ, Secunda C, Spridik K, Blair HC., Free PMC Article | 06/22/2019 |
| We observed mRNA correction rates up to 63%, restoration of phenylalanine hydroxylase (PAH) enzyme activity, and reversion of the light fur phenotype in Pah(enu2) mice. Our findings suggest that targeting genetic diseases in vivo using AAV-mediated delivery of base-editing agents is feasible, demonstrating potential for therapeutic application. | Treatment of a metabolic liver disease by in vivo genome base editing in adult mice.
Villiger L, Grisch-Chan HM, Lindsay H, Ringnalda F, Pogliano CB, Allegri G, Fingerhut R, Häberle J, Matos J, Robinson MD, Thöny B, Schwank G. | 05/11/2019 |
| We demonstrate that kinetically instable and aggregation-prone variant Pah proteins trap BH4, shifting the pool of free BH4 towards bound BH4. Interference of PAH protein misfolding with metabolite-based control of l-phenylalanine turnover suggests a mechanistic link between perturbation of protein homeostasis and disturbed regulation of metabolic pathways. | Secondary BH4 deficiency links protein homeostasis to regulation of phenylalanine metabolism.
Eichinger A, Danecka MK, Möglich T, Borsch J, Woidy M, Büttner L, Muntau AC, Gersting SW. | 02/16/2019 |
| We propose that CNS monoamine deficiency may be the cause of the partially reversible adverse behavioral effects associated with chronic HPA in Pah(enu2) mice, but that phenylalanine-reducing treatments initiated during adulthood are unable to correct the neuropathology and attendant cognitive deficits that develop during juvenile life in late-treated Pah(enu2/enu2) mice | Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies and partially improves behavioral performance in adult phenylketonuric mice.
Winn SR, Scherer T, Thöny B, Ying M, Martinez A, Weber S, Raber J, Harding CO., Free PMC Article | 12/22/2018 |
| we assessed DNA methylation patterns in brain tissues using methylated DNA immunoprecipitation and paired end sequencing in adult PAH(enu2) animals maintained under either continuous dietary Phe restriction or chronic hyperphenylalaninemia. Heterozygous PAH(enu2/WT) litter mates served as controls for normal Phe exposure | DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria.
Dobrowolski SF, Lyons-Weiler J, Spridik K, Vockley J, Skvorak K, Biery A., Free PMC Article | 12/9/2017 |
| These observations support the proposition that differences in phenylalanine hydroxylase activity underlie the variation in S-carboxymethyl-L-cysteine sulfoxidation and that no other enzyme is able to undertake this reaction. | Phenylalanine monooxygenase and the sulfur oxygenation of S-carboxymethyl-L-cysteine in mice.
Vandenbossche E, Lucas C, Mistry L, Garfield E, Mitchell SC, Steventon GB. | 10/29/2016 |
| A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice | Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice.
Yew NS, Dufour E, Przybylska M, Putelat J, Crawley C, Foster M, Gentry S, Reczek D, Kloss A, Meyzaud A, Horand F, Cheng SH, Godfrin Y. | 03/22/2014 |
| high levels of Phe, such as in phenylketonuria, are unlikely to directly induce brain hypomyelination, suggesting involvement of alternative mechanisms in this myelination defect | Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites.
Schoemans R, Aigrot MS, Wu C, Marée R, Hong P, Belachew S, Josse C, Lubetzki C, Bours V., Free PMC Article | 07/26/2010 |
| phenylalanine concentration regulates the activity of PAH in the hph-1 mouse and that this acts via a mechanism that includes phosphorylation of the PAH molecule | In vivo regulation of phenylalanine hydroxylase in the genetic mutant hph-1 mouse model.
Gunasekera RS, Hyland K. | 01/25/2010 |
| Tetrahydrobiopterin protects PAH activity in vivo. | Tetrahydrobiopterin protects phenylalanine hydroxylase activity in vivo: implications for tetrahydrobiopterin-responsive hyperphenylalaninemia.
Thöny B, Ding Z, Martínez A. | 01/21/2010 |
| low level of phenylalanine clearance was observed in mice expressing PAH and GTP-CH from the keratin 14 promoter | Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin.
Christensen R, Alhonen L, Wahlfors J, Jakobsen M, Jensen TG. | 01/21/2010 |