Disease relevance of Edpm5

• The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat pituitary tumor [1].
• Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains [1].
• Rat obesity gene fatty (fa) maps to chromosome 5: evidence for homology with the mouse gene diabetes (db) [2].
• In addition, 2 loci that were not associated with arthritis were found to regulate serum levels of the acute-phase protein Apr1 (acute-phase response 1) at the telomeric end of chromosome 12 and Apr2 on chromosome 5 [3].
• High incidence of allelic loss on chromosome 5 and inactivation of p15INK4B and p16INK4A tumor suppressor genes in oxystress-induced renal cell carcinoma of rats [4].

High impact information on Edpm5

• We identified a highly significant QTL on rat chromosome 5 with a lod score of 16.6 which accounts for 67% of the total variance, co-localizes with the genes encoding atrial and brain natriuretic factor and is blood pressure independent [5].
• Human dopamine D1 receptor encoded by an intronless gene on chromosome 5 [6].
• The ET2 locus was assigned to rat chromosome 5 [7].
• Two of the cell lines analyzed exhibited alterations involving losses of part or all of one member of the chromosome 5 pair [8].
• Early-passage clone 7 cells exhibited chromosome 5 monosomy, while late-passage cells contained one normal chromosome 5 and a derivative (5q12q) [8].

Chemical compound and disease context of Edpm5

• The present study examined whether transfer of overlapping regions of chromosome 5 that include (4A+) or exclude the cytochrome P-450 (CYP) 4A genes from the Lewis rat alters the renal production of 20-hydroxyeicosatetraenoic acid (20-HETE) and/or the development of hypertension in congenic strains of Dahl salt-sensitive (S) rats [9].
• In genetic studies of familial calcium pyrophosphate dihydrate deposition disease, a region on the short arm of chromosome 5 was found to be genetically linked to the phenotype displayed by several of these families [10].

Biological context of Edpm5

• To investigate the role of Edpm5 in the development of these tumors, we have generated a novel congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat chromosome bearing Edpm5 from BN into the F344 strain background [1].
• Hence at least one gene that has a large impact, directly or indirectly, on the switch to angiogenic phenotype must reside within the chromosomal interval that is the Edpm5 quantitative trait locus [1].
• Through use of these strains, we find that Edpm5 specifically regulates the switch to angiogenic phenotype, independent of neoplasia [1].
• Recently the putative tumor suppressor gene p16INK4 was mapped to human chromosome 9p21, which is homologous to rat chromosome 5 [11].
• The gene for this LAP/LERP protein comprises at least 26 exons located on the long arm of chromosome 5 [12].

Anatomical context of Edpm5

• Analysis of hybrid cell panels indicates that the human PAM gene is situated on the long arm of chromosome 5 [13].
• Rat chromosome 5 (q22-23) contains elements that control cell morphology and interactions with the extracellular matrix: a study of normal fibroblast x malignant hepatoma cell hybrids [14].
• Starting with an expressed DNA fragment retrieved by exon trapping from pooled human BAC clones mapped to the short arm of chromosome 5, we identified a human nucleoporin cDNA sequence by PCR from a human testis cDNA library [15].
• The chromosome 2 LORR QTL may confer variation in ethanol metabolism, whereas the chromosome 5 LORR/BECrrr QTL likely mediates central nervous system ethanol sensitivity [16].

Associations of Edpm5 with chemical compounds

• In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogen-dependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level [17].
• The male-specific QTL on chromosome 5 appeared to overlap with previously reported QTLs for stroke-associated phenotypes, but an identical gene (or genes) appeared unlikely to control these and the cholesterol traits simultaneously [18].
• In both (ACI x COP)F(2) and (COP x ACI)F(2) populations, we find strong evidence for a major genetic determinant of susceptibility to E2-induced mammary cancer on distal rat chromosome 5 [19].
• Mapping of rat prostatic binding protein genes C1, C2, and C3 to rat chromosome 5 by in situ hybridization [20].
• In addition, we identified novel interactions between Nidde6 (chromosome 1) and 7/of (chromosome 13), and Nidde8 (chromosome 5) and 9/of (chromosome 19), which is involved in fasting glucose levels but not postprandial glucose levels [21].

Other interactions of Edpm5

• Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker [22].
• The Mcs5 subloci are currently localized to 1.0, 7.5, and 4.5 Mb of rat chromosome 5, and the orthologous regions are on human chromosome 9 and mouse chromosome 4 [23].
• More recently, we have mapped to rat chromosome 5 a strong genetic modifier of susceptibility to E2-induced mammary cancers, termed estrogen-induced mammary cancer 1 (Emca1), and have identified potential Emca1 candidate genes [24].
• Linkage mapping of the endothelin-converting enzyme gene (Ednce) to rat chromosome 5 [25].
• In this backcross, the QTL Edpm5 (_e_strogen-_d_ependent _p_ituitary _m_ass on Chromosome 5) has a significant effect on MMP-9 levels, with inheritance of the BN allele of Edpm5 correlating with suppression of estrogen-dependent MMP-9 expression [26].

Analytical, diagnostic and therapeutic context of Edpm5

• Regional mapping, performed by examination of a series of chromosome 5 deletion mutants and by in situ hybridization to human chromosomes indicates that the two genes are not tightly clustered [27].
• As possible candidate tumor suppressor genes on chromosome 5, p15INK4B and p16INK4A were investigated for genetic alteration and aberrant methylation by Southern blot, PCR/SSCP/ sequencing and methylation-specific PCR [4].
• Using Southern blotting, we tested whether any of several gene probes, known to correspond to DNA sequences in rat chromosome 5, were homologous to sequences in the deletion [28].
• We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5 [29].
• Linkage mapping of rat chromosome 5 markers generated from chromosome-specific libraries [30].

References