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• W3103875509 abstract "Abstract Alkaptonuria (AKU) is caused by homogentisate 1,2‐dioxygenase (HGD) deficiency. This study aimed to determine if HGD and other enzymes related to tyrosine metabolism are associated with the location of ochronotic pigment. Liver, kidney, skin, bone, brain, eyes, spleen, intestine, lung, heart, cartilage, and muscle were harvested from 6 AKU BALB/c Hgd −/− (3 females, 3 males) and 4 male C57BL/6 wild type (WT) mice. Hgd , 4‐hydroxyphenylpyruvate dioxygenase ( 4 ‐ Hppd ), tyrosine hydroxylase ( Th ), and tyrosinase ( Tyr ) mRNA expression was investigated using qPCR. Adrenal gland and gonads from AKU Hgd tm1a −/− mice were LacZ stained, followed by qPCR analysis of Hgd mRNA. The liver had the highest expression of Hgd , followed by the kidney, with none detected in cartilage or brain. Low‐level Hgd expression was observed within developing male germ cells within the testis and epididymis in Hgd tm1a −/− . 4‐ Hppd was most abundant in liver, with smaller amounts in kidney and low‐level expression in other tissues. Th was expressed mainly in brain and Tyr was found primarily in the eyes. The tissue distribution of both Hgd and 4‐ Hppd suggest that ochronotic pigment in AKU mice is a consequence of enzymes within the liver, and not from enzymatic activity within ochronotic tissues. Excessive accumulation of HGA as ochronotic pigment in joints and other connective tissues originates from the circulation and therefore the extracellular fluid. The tissue distribution of both Th and Tyr suggests that these enzymes are not involved in the formation of HGA‐derived ochronotic pigment." @default.
• W3103875509 created "2020-11-23" @default.
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• W3103875509 date "2020-11-12" @default.
• W3103875509 modified "2023-10-11" @default.
• W3103875509 title "Expression of tyrosine pathway enzymes in mice demonstrates that homogentisate 1,2‐dioxygenase deficiency in the liver is responsible for homogentisic acid‐derived ochronotic pigmentation" @default.
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• W3103875509 doi "https://doi.org/10.1002/jmd2.12184" @default.
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