Expression of the Cystathionine β Synthase (CBS) Gene During Mouse Development and Immunolocalization in Adult Brain

Abstract

Hyperhomocysteinemia, caused by a lack of cystathionine β synthase (CBS), leads to elevated plasma concentrations of homocysteine. This is a common risk factor for atherosclerosis, stroke, and possibly neurodegenerative diseases. However, the mechanisms that link hyperhomocysteinemia due to CBS deficiency to these diseases are still unknown. Early biochemical studies describe developmental and adult patterns of transsulfuration and CBS expression in a variety of species. However, there is incomplete knowledge about the regional and cellular expression pattern of CBS, notably in the brain. To complete the previous data, we used in situ hybridization and Northern blotting to characterize the spatial and temporal patterns of Cbs gene expression during mouse development. In the early stages of development, the Cbs gene was expressed only in the liver and in the skeletal, cardiac, and nervous systems. The expression declined in the nervous system in the late embryonic stages, whereas it increased in the brain after birth, peaking during cerebellar development. In the adult brain, expression was strongest in the Purkinje cell layer and in the hippocampus. Immunohistochemical analyses showed that the CBS protein was localized in most areas of the brain but predominantly in the cell bodies and neuronal processes of Purkinje cells and Ammon's horn neurons.

A functional variant in the cystathionine β-synthase gene promoter significantly reduces congenital heart disease susceptibility in a Han Chinese population

“…These affected CHD sub-classifications are highly consistent with the CBS expression pattern in both human and mouse embryos [10,11]. CBS mRNA was observed in a 36-day-old human embryo (CS15) in the endocardium cells and was additionally found in cells derived from the neural crest forming the myocardial walls of the bulbus cordis [11].…”

“…Then, CBS mRNA was detectable in the endocardial tissue and in the atrial and ventricle myocardial walls at a later stage [11]. In the mouse cardiovascular system, CBS expression was additionally detected from E12.5 in the endocardial cells [10].…”

“…CBS deficiency is the most common cause of classical homocystinuria (HCU, OMIM236200), an inherited autosomal recessive metabolic disease [9]. Although CBS is presented at a low level in the fetus compared to adults, its expression is concentrated in the neural and cardiac tissues, especially in the endocardium cells, which implies a potential function of CBS in embryo cardiac development [10,11]. The few association studies that focused on the CBS coding region variants and CHD risk obtained negative results [12,13].…”

Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency

“…During the first 2 weeks of postnatal life, there is an exponential decrease of folate in the mouse brain, with lower levels of polyglutamylated folates, indicating high turnover and demand for folates in early extrauterine life [27]. In contrast with the postnatal decreases in activity of the remethylation enzymes, the rate-limiting enzyme of the trans-sulphuration pathway, cystathionine β-synthase, shows decreased activity in the cerebrum during late fetal stages, increases after birth and peaks during cerebellar development [28]. The activity of the last enzyme of the trans-sulphuration pathway from methionine to cysteine, cystathionase, increases gradually in rat brain over 4 weeks after birth [29].…”

Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria

“…Moreover, it perturbs the methylation cycle, such as the intracellular accumulation of S-adenosyl homocysteine, which has consequences for cell metabolism . Elevated homocysteine levels are a potential risk factor for cardiovascular disease (Guba et al, 1996;Robert et al, 2003b), and several studies have…”