Disease relevance of Prh1

• Clones containing two nonallelic PRP genes (MP2 and M14) were isolated from cosmid and phage libraries of CD-1 mouse genomic DNA [1].
• These results suggest that a gene or genes within the natural killer gene complex, adjacent to the Prp locus, determine strain variations in resistance to lethal ectromelia virus infection [2].
• The association between the Prp locus and susceptibility to lethal mousepox also held for N2 male mice that were castrated as neonates, which increased the percentage that were susceptible to 40 [2].
• Loss of intracisternal A-type retroviral particles in BL6 melanoma cells transfected with MHC class I genes [3].
• Mutations within LMNA, encoding A-type nuclear lamins, are associated with multiple tissue-specific diseases, including Emery-Dreifuss (EDMD2/3) and Limb-Girdle muscular dystrophy (LGMD1B) [4].

High impact information on Prh1

• By introducing mutations, we found that the three genes gag, prt and pol are all required for retrotransposition and identified the IAP gene products by electron microscopy in the form of intracellular A-type particles in the transfected cells [5].
• These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies [6].
• A second A-type cyclin, cyclin A1 has been described recently which, in the mouse, is expressed in germ cells but not somatic tissues [7].
• Here we describe the derivation of mice carrying an autosomal recessive mutation in the lamin A gene (Lmna) encoding A-type lamins, major components of the nuclear lamina [8].
• In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes [9].

Chemical compound and disease context of Prh1

• Enhancing effect of hydrocortisone acetate administration on the content of A-type particles in Ehrlich ascites tumor [10].
• PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas [11].
• 1. The RNA-dependent DNA polymerase associated with cytoplasmic A-type particles of murine mammary tumor virus was isolated to near homogeneity by a procedure which includes dissociation of proteins from RNA by centrifugation in a step gradient of cesium chloride, followed by an affinity chromatography on poly(rC)-agarose column [12].
• A new cell line of murine myeloid leukemia with A-type phosphoglycerate kinase as marker isoenzyme [13].
• Native hGH that had been purified by DEAE-cellulose chromatography (A-type; 1.8 IU/mg) produced fasting hyperglycemia and glucose intolerance in the ob/ob mouse when injected subcutaneously at doses of 50 micrograms/day or greater for 3 days [14].

Biological context of Prh1

• The bitterness tasting gene Soa is very closely linked to Prp on chromosome 6 (no recombinants among 67 backcross progeny) [15].
• Sucrose octaacetate avoidance in nontaster mice is not enhanced by two type-A Prp transgenes from taster mice [16].
• We have aligned yeast artificial chromosome (YAC) inserts in a contig spanning the interval between the Ly49 and Prp gene clusters [17].
• The DNA sequence analysis presented in this report suggests that genes M14 and MP2 (Ann, D. K., and Carlson, D. M. (1985) J. Biol. Chem. 260, 15863-15872) arose via a gene duplication of a common ancestor [1].
• Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis [18].

Anatomical context of Prh1

• Transgene expression varied among the founder lines, but SWR-like expression levels, higher than background FVB expression levels, were found in submandibular gland tissue of adult transgenic mice from two MP2 lines and one M14 line [16].
• The discoveries of at least eight human diseases arising from mutations in LMNA, which encodes the nuclear A-type lamins, have revealed the nuclear envelope as an organelle associated with a variety of fundamental cellular processes [19].
• Similarly, normal muscle cells that have been RNA interference (RNAi) down-regulated for either A-type lamins or emerin have impaired differentiation potentials [4].
• In spinal cord dorsal horn neurons, A-type currents are modulated by extracellular signal-regulated kinases (ERKs), which mediate central sensitization during inflammatory pain [20].
• CONCLUSIONS: DeltaF508 CFTR can be activated to levels 4% of wild-type when the combination of protein kinase A type II activators and phosphodiesterase class I and III inhibitors are used in murine jejunum [21].

Associations of Prh1 with chemical compounds

• To assess the latter possibility, two type-A, proline-rich protein genes (MP2 and M14), situated approximately 30 kb apart at the Prp locus, were separately transferred from an SOA-taster inbred strain (SWR) to an SOA-nontaster inbred strain (FVB) [16].
• Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current [18].
• Moreover, GABA, acting through A-type receptors, can both phase shift and synchronize clock cells [22].
• Bone marrow cells were harvested after injection of 5-fluorouracil from C57BL/6-Pgk-1b/Pgk-1a female mice in which each stem cell had either A-type PGK or B-type PGK due to the random inactivation of one or two X chromosomes [23].
• To understand how the laminopathies arise from different mutations in a single gene, we derived a mouse line by homologous recombination expressing the Lmna-N195K variant of the A-type lamins with an asparagine-to-lysine substitution at amino acid 195, which causes DCM in humans [24].

Physical interactions of Prh1

• Calsenilin interacts with presenilins, DREAM is a calcium-regulated transcriptional repressor and KChIP3 binds and modulates A-type potassium channels [25].
• Previous studies have indicated that A-type lamins interact with the retinoblastoma protein (pRB) [26].

Regulatory relationships of Prh1

• Both A-type currents in cultured hippocampal neurons and A-type currents recorded from HEK 293 cells transiently expressing recombinant Kv4.2 channels were selectively inhibited by T. leblondi venom [27].
• The AE1 gene is expressed in erythrocytes and the A-type intercalated cells of the kidney distal collecting duct [28].
• The mechanisms of inactivation gating of the neuronal somatodendritic A-type K(+) current and the cardiac I(to) were investigated in Xenopus oocyte macropatches expressing Kv4.1 and Kv4.3 channels [29].

Other interactions of Prh1

• Localization on a physical map of the NKC-linked Cmv1 locus between Ly49b and the Prp gene cluster on mouse chromosome 6 [17].
• We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8) [30].
• In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced [18].
• Two other markers, Ea-10 and Es-12, that were previously unassigned to a chromosome are closely linked to Prp genes in the mouse [31].
• Here, we report that A-type lamins are essential for the inhibition of fibroblast proliferation by TGF-beta1 [32].

Analytical, diagnostic and therapeutic context of Prh1

• Restriction mapping established the physical lineage of PRP genes MP2 and M14, and they are tandemly arrayed [1].
• We show here, by combining multiplex and quantitative real-time single-cell RT- PCR with slice patch-clamp electrophysiology, that an A-type potassium channel mediated by Kv4.3 and KChip3 subunits has a key role in pacemaker control [33].
• Based on the 1D 1H NMR spectra, the proteins are classified into four groups, "A" to "D." A-type proteins are candidates for structure determination by NMR or crystallography; "B"-type are earmarked for crystallography; "C" indicates folded globular proteins with broadened line shapes; and "D" are nonglobular, "unfolded" polypeptides [34].
• This is the first description of a retrovirus genome in rabbits, and sequence analysis shows that it is related to but distinct from A-type retroelements of mice and other rodents [35].
• We used conventional voltage-clamp techniques to identify and characterize A-type currents in myocytes isolated from the murine antrum [36].

References