Disease relevance of Aldoc

• Aldolase C mRNA expression is developmentally regulated in the fetal lung, rapidly downregulated in the newborn lung at birth, and inducible in the adult lung when exposed to hypoxia [1].
• In the posterior lobe vermis these blebs are seen in both transverse and sagittal sections, are symmetrical about the midline, reproducible between neighboring sections and between individuals, and bear a constant relationship to the Purkinje cell bands as revealed by zebrin II immunocytochemistry [2].

High impact information on Aldoc

• With the exception of cerebellar Purkinje cells, aldolase A mRNA is found in neurons; aldolase C message is detected in astrocytes, some cells of the pia mater, and Purkinje cells [3].
• Thus, with the exception of Purkinje cell expression, the behavior of the full-length transgene mimics the endogenous aldolase C gene [3].
• We isolated aldolase C genomic clones that span the entire protein coding region from 1.5 kb 5' to the transcription start site to 0.5 kb 3' to the end of the last exon [3].
• Part of the striped cerebellar topography is disrupted due to cell death and, in addition, many of the surviving PCs, that would normally adopt a zebrin II-negative phenotype, transdifferentiate to Zebrin II-positive, an unprecedented finding suggesting that Ebf2 is required for the establishment of a proper cerebellar cortical map [4].
• We have examined three markers of cerebellar compartmentation in En-2 mutant mice: the Zebrin II and Ppath monoclonal antibodies and the transgene L7lacZ [5].

Biological context of Aldoc

• Zebrin II/aldolase C gene expression is thus regulated at the level of transcription (or mRNA stability) [6].
• Aldolase C/zebrin gene regulation by prolactin during pregnancy and lactation [7].
• Taken together, our study localizes a Purkinje cell enhancer to a small 5' region of the aldolase C gene and illustrates that the element(s) responsible for the normal anatomically complex pattern of aldolase C expression are separate from those conferring cell-type specificity [8].
• Monoclonal anti-human aldolase C antibodies that react to the isozyme group-specific sequences and generally conserved sequences of human aldolase C1 [9].
• A chloramphenicol acetyltransferase gene directed by either 800 or 115 base pairs of aldolase C 5'-flanking sequences is tissue specifically expressed in transgenic mice, but the level of expression is very low [10].

Anatomical context of Aldoc

• Hypoxia results in an HIF-1-dependent induction of brain-specific aldolase C in lung epithelial cells [1].
• We propose therefore that the chromatin structure around the aldolase C promoter is accessible in fetal tissues, then remains open in the adult brain, where the gene is very active, as well as in tissues in which it is practically inactive [10].
• Identification of aldolase C compartments in the mouse cerebellar cortex by olivocerebellar labeling [11].
• We show that aldolase C messenger expression in the hippocampus is restricted to CA3 neurons [12].
• The anti-BW6 staining pattern was complementary to the zebrin II bands, the zebrin II- Purkinjke cells having BW6+ dendrites [13].

Associations of Aldoc with chemical compounds

• Nine monoclonal mouse anti-human aldolase C antibodies, mAbs A4, A8, B4, B7, B8, C1, D9, E10, and H1, were isolated and characterized [9].
• This level is greatly increased when the transgene consists of a chloramphenicol acetyltransferase hybrid gene directed by 5.5 kilobases of aldolase C 5'-flanking sequences [10].

Regulatory relationships of Aldoc

• At this stage of development, the borders of the OL-protocadherin-positive Purkinje cell segments coincide with the borders of Purkinje cell segments that express zebrin II, a marker for the "late-onset" parasagittal banding pattern which persists in the adult cerebellum [14].

Other interactions of Aldoc

• The hgn locus was linked to Aldoc (aldolase c) and whn (winged helix of nude), and located in a 0.34-cM region between D10Rat30 and D10Rat68 [15].
• The Purkinje cells, identified by anti-zebrin II in the adult or anti-calbindin in the new born mdab1-1 mutant cerebellum, form a parasagittal banding pattern, similar to but distorted compared with the wild-type design [16].
• In the adult weaver (wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is abnormal, consistent with the absence of a central zone (approximately lobules VI/VII) [17].
• Interestingly, the parasagittal expression pattern of HNK-1 is different from those reported with several other markers such as zebrin II/aldolase C and the small heat shock protein HSP25 [18].
• The zinc finger transcription factor zif268/egr-1, also known to recognize a (G+C)-rich consensus site, did not, however, bind to the (G+C)-rich motif of the aldolase C promoter, nor could it stimulate transcription in transactivation assays from this control region [19].

Analytical, diagnostic and therapeutic context of Aldoc

• Further, in situ hybridization of antisense aldolase C riboprobe shows that the accumulation of zebrin II/aldolase C mRNA corresponds to the pattern of the zebrin antigen in Purkinje cells [6].
• First, zebrin II-negative Purkinje cells disappear, to leave survivors aligned in stripes that closely resemble the pattern revealed by using zebrin II immunocytochemistry [20].
• Aldolase C mRNA is detected by Northern blot in all fetal tissues in rat; it is very abundant in the adult brain and undetectable in the other adult tissues [10].
• In gel-retardation assays, two major DNA-protein complexes were detected with the (G+C)-rich element of the aldolase C promoter used as a DNA probe and nuclear extracts from brain and liver as a source for DNA-binding proteins [19].

References