Complex response to physiological and drug-induced hepatic heme demand in monoallelic ALAS1 mice.

ABSTRACT: Regulation of 5-aminolevulinate synthase 1 (ALAS1) for nonerythroid heme is critical for respiration, cell signaling mechanisms and steroid/drug metabolism. ALAS1 is induced in some genetic disorders but unlike other genes in the heme pathway, a gene variant of ALAS1 associated with inherited disease has not been reported. BALB/c mice carrying a null ALAS1 allele caused by a βGEO insert were developed and used to determine the consequences of heme demand of a semi gene copy number. Homozygous disruption of ALAS1 (-/-) was lethal for embryo development post day 6.5 but expression in heterozygotes (+/-) was sufficient for the number of offspring and survival. In both wild type (WT +/+) and +/- mice expression of ALAS1 RNA was greatest in liver and harderian gland and much lower in kidney, lu

SUBMITTER: Vagany V 

PROVIDER: S-EPMC8639769 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature