CLN-1 and CLN-5, genes for infantile and variant late infantile neuronal ceroid lipofuscinoses, are expressed in the embryonic human brain

Abstract

Mutations in the CLN-1 and CLN-5 genes underlie the infantile, and Finnish variant of the late-infantile, neuronal ceroid lipofuscinoses, respectively. These disorders are characterized by a massive neuronal death early in childhood. We have studied mRNA and protein expression of CLN-1 and CLN-5 in embryonic human brains. The spatial and temporal distributions of CLN-1 and CLN-5 were similar in the embryonic human brain. Both genes are expressed at the beginning of cortical neurogenesis, and this expression increases as cortical development proceeds. In the developing cortical plate, expression is found in postmitotic migrating neuroblasts and neuroblasts that have completed migration. Expression was intense also in cells of the thalamus as well as in the future Purkinje cell layer of the cerebellum. These findings indicate that expression of CLN-1 and CLN-5 may be significant for development of a wide range of maturating neurons.

Neuronal ceroid lipofuscinosis genes, CLN2, CLN3 and CLN5 are spatially and temporally co-expressed in a developing mouse brain

“…From the prenatal day E14.5 to the postnatal day P1, CLN mRNAs and proteins were detected in the thalamus, choroid plexus and in the endothelial epithelium of a developing mouse brain. This corresponds somewhat to the expression patterns of CLN1 and CLN5 proteins observed in developing human fetuses (Heinonen et al, 2000). In humans, expression of CLN5 protein is detected in ventricular zones as early as on embryonic day 37.…”

“…CLN3 (Sleat et al, 1997;Järvelä et al, 1998) and CLN5 (Heinonen et al, 2000), encode lysosomal membrane proteins of unknown function. Recent data suggests, however, that expression pattern of CLN proteins in the brain differs strikingly from that in the peripheral tissues.…”

“…Recent data suggests, however, that expression pattern of CLN proteins in the brain differs strikingly from that in the peripheral tissues. PPT1, for example, is localized in neurons into synaptosomes and synaptic vesicles (Vesa et al, 1995;Heinonen et al, 2000;Lehtovirta et al, 2001). CLN3, as well, is targeted to neuronal synapses (Järvelä et al, 1998;Luiro et al, 2001).…”

Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1) – distinct characteristics in neurons

“…PC12 cells were cultured on collagen coated dishes in RPMI 1640 medium supplemented with 10% horse serum, 5% fetal calf serum and antibiotics. Mouse hippocampal and cortical neurons as well as mouse fibroblasts were prepared from wild type C57/BL mouse embryos and maintained as previously described [6,45]. For the glycosylation assays and immunofluorescence, COS-1 and HeLa cells were single transfected similarly using mutated (M1I, G108R, Y109D, Q177E, and V181M) and wild type PPT1-pCMV5 constructs.…”

The neuronal ceroid lipofuscinosis Cln8 gene expression is developmentally regulated in mouse brain and up-regulated in the hippocampal kindling model of epilepsy

“…Mouse Cln3 is expressed in adult mice throughout the brain, and in the hippocampus the most prominent expression is detected in the granular cell layer of the dentate gyrus and pyramidal cells [28]. In addition, human CLN1 and CLN5 genes are expressed at the beginning of neurogenesis in embryonic human brains [33]. This expression increases as brain development proceeds.…”