Disease relevance of Crabp1

• The regulation of mouse cellular retinoic acid-binding protein-I (CRABP-I) gene expression by the retinoids and thyroid hormones was examined, by using a beta-galactosidase (lacZ) reporter gene and a CRABP-I specific antibody, in transgenic mouse embryos and a mouse embryonal carcinoma cell line P19 [1].
• Mouse cellular retinoic acid binding protein: cloning, complementary DNA sequence, and messenger RNA expression during the retinoic acid-induced differentiation of F9 wild type and RA-3-10 mutant teratocarcinoma cells [2].
• Cell lines that contained CRABP included S91 and B16 melanomas; Mm5mT and DMBA No. 8 mammary adenocarcinomas; BW5147, BW5147.RicR, and P3 neoplastic lymphoid cells; F361.2 (a hybrid cell line obtained by fusion of MSV3T3 and BW5147); MSV3T3 sarcoma; and RAW8 lymphosarcoma [3].
• In addition, the generated transgenic mice also present expression of the transgene in the pancreas and develop pancreatic carcinomas, suggesting that overexpression of the cellular retinoic acid-binding protein is the cause of the tumors [4].
• The dorso-ventral asymmetry extends also to the cellular retinoic acid binding protein CRABP I, which first appears in the early differentiating ganglion cells in central retina and in the later embryo shows transiently a ventro-dorsally receding pattern of expression [5].

High impact information on Crabp1

• Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse [6].
• These results indicate that all three RARs and CRABP have specific functions during morphogenesis and differentiation of the mouse limb [6].
• A retinoic acid gradient, possibly amplified by a graded distribution of cellular retinoic acid-binding protein (CRABP), could provide positional information across the antero-posterior axis of the chick limb bud [6].
• Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220 [7].
• The cellular retinoic acid binding protein I gene is induced by thyroid hormone (T3) through a T3 response element (TRE) approximately 1 kb upstream of the basal promoter [7].

Chemical compound and disease context of Crabp1

• Demethylation in the 5'-flanking region of mouse cellular retinoic acid binding protein-I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells [8].
• Cellular retinol (CRBP) and retinoic acid binding proteins (CRABP) were measured in normal (C57Bl) and Murine Mammary Tumor Virus (MuMTV)-induced murine mammary tumor cells (C57BlfRIII) grown in monolayer culture [9].
• It has been proposed that cellular retinoic acid binding protein is essential for retinoid-induced differentiation of embryonal carcinoma line PCC4.aza1R [10].
• The effect of dibutyryl cyclic AMP and butyrate on F9 teratocarcinoma cellular retinoic acid-binding protein activity [11].
• The bifunctional analogues induce differentiation of mouse embryonal carcinoma cells, and those analogues that have a free carboxyl group bind to cellular retinoic acid binding protein [12].

Biological context of Crabp1

• Both CRABP transcripts are present in embryonic structures from the earliest stages studied and exhibit specific patterns of distribution, suggesting that the two retinoic acid (RA) binding proteins perform different functions during mouse embryogenesis [13].
• The transcript distribution of CRABP I and II is discussed in relation to the teratogenic effects of RA, and compared to the RA-sensitive pattern of expression of other important developmental genes [13].
• Expression of the cellular retinoic acid binding protein I (CRABPI) is restricted during development in Kölliker's organ whilst cellular retinol binding protein II (CRBPII) is only visible after birth with a ubiquitous distribution in most regions of the cochlea including nervous components [14].
• Throughout placentation, the expression patterns of the CRABP I and II genes partly overlap in the decidual tissue and the vacuolar zones of the decidua, suggesting a role for these binding proteins in sequestering free retinoic acid from maternal blood, thus regulating its availability to the embryo [15].
• A role of thyroid hormones in CRABP-I gene expression and vitamin A metabolism in animals is discussed [1].

Anatomical context of Crabp1

• The CRABP I transcript distribution correlates well with structures known to be targets of excess retinoid-induced teratogenesis (e.g. neural crest cells and hindbrain), suggesting that cells expressing CRABP I are those that cannot tolerate high levels of RA for their normal developmental function [13].
• The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons [16].
• We suggest that the transcriptional activator retinoic acid (RA), takes part in gene regulation after peripheral nerve injury and that RA signalling is activated via the cellular retinoic acid binding protein (CRABP)-II and cellular retinol binding protein (CRBP)-I [17].
• In addition to the two known acidic RA-binding proteins CRABP I and II, the cerebellum expressed a third RA-binding protein distinguishable by its neutral isoelectric point; the same binding protein was also detected in the olfactory bulb, kidney and testes [18].
• The CRABP-lacZ reporter gene expression recapitulated the expression pattern of endogenous CRABP-I in the developing central nervous system [1].

Associations of Crabp1 with chemical compounds

• For instance, expression of CRABP I in the migrating cells that give rise to the olivary and pontine nuclei, which develop abnormally in conditions of retinoid excess, is consistent with observations from a variety of other systems indicating that CRABP I limits the access of RA to the nuclear receptors in normal physiological conditions [19].
• These data suggest that proline isomerization may not be responsible for the slowest folding phase of CRABP I [20].
• Regulation of the mouse cellular retinoic acid-binding protein-I gene by thyroid hormone and retinoids in transgenic mouse embryos and P19 cells [1].
• In experiments designed to alter the thyroid hormone status in animals it was demonstrated that both the reporter gene and the endogenous CRABP-I expression were reduced by triiodothyronine injection and were elevated in a hypothyroidic condition induced by feeding with iodine-deficient diet supplemented with 6-propyl-2-thiouracil [1].
• Subconfluent cultures of MEPM cells were treated for several days with phosphorothioate modified 18-mer oligonucleotides antisense to CRABP-I or CRABP-II and then with all-trans-retinoic acid at a concentration of 3.3 microM or 0.33 microM for 5 or 22 h [21].

Physical interactions of Crabp1

• We have previously shown that both transforming growth factor-beta (TGF-beta) and retinoic acid (RA) regulate the expression of cellular retinoic acid binding proteins (CRABP) I and II and TGF-beta 3 mRNAs in primary cultures of murine embryonic palate mesenchymal (MEPM) cells [22].

Regulatory relationships of Crabp1

• Furthermore, heat- or acid-activated CM also inhibited CRABP-I and RA-induced RAR-beta expression [22].
• Antisense oligonucleotides to CRABP-I partially inhibited the RA-induced TGF-beta 3, RAR-beta, and tenascin mRNA expression [21].
• Most mesenchymal cells of the limbs and craniofacial structures did not express detectable levels of CRBP I but instead expressed cellular retinoic acid-binding protein I (CRABP I) [23].
• However, BMP-2 down-regulated CRABP I message without affecting message stability [24].
• Stably transfected lines expressing elevated levels of CRABP-I exhibit an 80-90% reduction in the RA induced expression of retinoic acid receptor (RAR) beta, laminin B1, and collagen type IV (alpha 1) mRNAs at low exogenous RA concentrations, but this reduction is eliminated at higher RA concentrations [25].

Other interactions of Crabp1

• Differential distribution patterns of CRABP I and CRABP II transcripts during mouse embryogenesis [13].
• No CRABP or CRBP transcripts were observed in the auditory receptors [14].
• In situ hybridization with 35S-labelled RNA probes was used to study the distribution of transcripts of genes coding for the retinoic acid receptors, RAR-alpha, -beta and -gamma, and the cellular binding proteins for retinoic acid (CRABP I) and retinol (CRBP I), in mouse embryos during the period of early morphogenesis [26].
• We describe the temporal and spatial expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT-PCR and immunohistochemistry [27].
• Receptor interacting protein 140 as a thyroid hormone-dependent, negative co-regulator for the induction of cellular retinoic acid binding protein I gene [28].

Analytical, diagnostic and therapeutic context of Crabp1

• As a step towards understanding the possible function for CRABP and CRBP in morphogenesis, we have used in situ hybridization to analyze their expression during mouse development [29].
• Use of organelle-specific fluorochromes indicated that CRABP immunofluorescence overlaid exactly with the pattern of the mitochondrial-specific fluorochrome [30].
• The levels of CRBP and CRABP were in the ranges 15-3,400 and 4-1,290 pmol per 10(9) cells, respectively, as determined by sucrose gradient centrifugation [3].
• Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein [31].
• Western blot analysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea [32].

References