Disease relevance of Ddx4

• We observe vasa vasorum density correlates highly with the extent of inflammatory cells, not the size of atheromas in apolipoprotein E-deficient mice [1].
• Mice with this genotype display a heritable phenotype of abnormal SMC proliferation in the central tail artery, vasa deferentia, seminal vesicles, prostate, and uterus, with the latter resembling uterine leiomyomatosis and prostatic hypertrophy [2].
• Delayed postnatal closure has been attributed to loss of vasa vasorum flow and ductus wall ischemia resulting from constriction in utero [3].
• Neuronal nitric oxide synthase mediates statin-induced restoration of vasa nervorum and reversal of diabetic neuropathy [4].
• Vasculitis involving testes, epididymides, and vasa deferentia is considered to be a rare disease but has often been reported in man [5].

Psychiatry related information on Ddx4

• In wild-type mice, AQP1 is expressed in kidney proximal tubule, thin descending limb of Henle, and descending vasa recta, where urine osmolality (Uosm) increases from 1000-1500 mOsm (before) to 2500-3500 mOsm after 36 hr of water deprivation [6].

High impact information on Ddx4

• Subsequently, Mvh is maintained until postmeiotic germ cells are formed [7].
• ICAM-1 is undetectable in mutant mice in contrast with normal mice, in which ICAM-1 is prominent in the endothelium of the vasa recta [8].
• Macrophages in the plaque and around vasa vasorum are reduced, but we detect no direct effect of angiostatin on monocytes [1].
• In adult tissues, Mvh transcripts were exclusively detected in testicular germ cells, in which Mvh protein was found to be localized in cytoplasm of spermatocytes and round spermatids including a perinuclear granule [9].
• We have focussed on mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and show that Dazl stimulates translation via the Mvh 3'-UTR [10].

Biological context of Ddx4

• A DEAD-family protein gene, Ddx4, encoding a murine homolog of Drosophila vasa maps to the distal end of mouse chromosome 13 [11].
• In male Mvh knockout mice, premeiotic germ cells arrest at the zygotene stage [12].
• Using morphological assessment and TUNEL we could show that in normal mice, regression of the primary vitreous, which includes the hyaloid artery, the vasa hyaloidea propria as well as the tunica vasculosa lentis, occurs via apoptotic cell death within 5 - 6 weeks after birth [13].
• Pharmacological studies on mouse isolated vasa deferentia demonstrated that all four analogs produce concentration-related inhibition of the twitch response and the order of potency is the same as the rank order of the affinities of these agonists for cannabinoid binding sites [14].
• In the present study, transgenic mice with a selective deficiency in UT-B (the urea transporter protein expressed in descending vasa recta and red blood cells), were used to evaluate the specific contribution of vascular urea recycling to overall urine-concentrating ability (UCA) [15].

Anatomical context of Ddx4

• In adult testis, MVH protein was localized in the cytoplasm of spermatogenic cells, including chromatoid bodies in spermatids, known to be a perinuclear nuage structure which includes polar granules that contain VASA protein in Drosophila [16].
• The artery also dissociated and fed an intramural plexus (vasa vasorum) of hepatic veins [17].
• Urea transporter UT-B has been proposed to be the major urea transporter in erythrocytes and kidney-descending vasa recta [18].
• Using in situ hybridization and immunohistochemistry, Tie-2 was detected in capillaries of the nephrogenic cortex, glomerular tufts, cortical interstitium, and medulla including vessels in the vasa recta [19].
• They showed reduced neovascularization in the liver sinusoids and kidney outer medulla vasa recta at P7, which most likely caused the ischemic necrosis observed by P14 in hepatocytes and renal tubular epithelia [20].

Associations of Ddx4 with chemical compounds

• 8 Normorphine (100 muM) did not reduce the noradrenaline output from vasa deferentia of C57/BL mice [21].
• 3. When vasa deferentia preincubated with [3H]-noradrenaline were stimulated with trains of 100 pulses delivered at 20 Hz, morphine 10 microM reduced significantly both evoked tritium overflow and evoked contractions [22].
• Vasa deferentia of mice were preincubated with 3H-noradrenaline and then superfused with a medium containing cocaine 10 microM and phentolamine 30 microM [23].
• 4 Morphine (2 muM) inhibited the contractions of the vasa deferentia from TO mice [21].
• 2. In isolated atria and vasa deferentia preloaded with [3H]-NA, electrical field stimulation caused [3H]-NA release, which was abolished by tetrodotoxin 0.5 microM and concentration-dependently inhibited by delta 9-THC or anandamide, 0.3-10 microM [24].

Other interactions of Ddx4

• Mouse RanBPM is a partner gene to a germline specific RNA helicase, mouse vasa homolog protein [12].
• Germ cell-specific ATP-dependent RNA helicase, the product of the mouse vasa homolog (Mvh), has been shown to play an essential role in the development of the male germ cell [12].
• Here, we show that the postmigratory germ cell-specific genes Mvh, Dazl and Scp3 are demethylated in germ cells, but not in somatic cells [25].

Analytical, diagnostic and therapeutic context of Ddx4

• Blood flow velocity was also measured with Doppler UBM imaging in the hyaloid artery, vasa hyaloidea propria, tunica vasculosa lentis, and retina [26].
• We used the murine ductus (which does not depend on vasa vasorum flow) to determine whether delayed postnatal closure may be because of mechanisms independent of in utero constriction [3].
• Vasa deferential sperm, caudal epididymal sperm and/or whole testes were extracted at various times after treatment with each agent [27].
• By calculating the number of spermatozoa produced by the mouse testis after vasectomy, and actually counting the number of spermatozoa present in the epididymides and vasa deferentia, the number of spermatozoa resorbed at different times was quantified [28].
• In mouse and guinea-pig vasa deferentia previously incubated with [3H]noradrenaline, electrical stimulation applied through parallel electrodes (transmurally) increased overflow of tritium 2- to 5-fold above the resting value [29].

References