Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify novel genes that are expressed specifically or preferentially in the cochlea, we constructed a cDNA library enriched for human cochlear cDNAs using a suppression subtractive hybridization technique. We analyzed 2640 clones by sequencing and BLAST similarity searches. One hundred and fifty-five different cDNA fragments mapped in nonsyndromic hearing impairment loci for which the causative gene has not been cloned yet. Approximately 30% of the clones show no similarity to any known human gene or expressed sequence tag (EST). Clones mapping in nonsyndromic deafness loci and a selection of clones that represent novel ESTs were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA derived from 12 human fetal tissues. Our data suggest that a quarter of the novel genes in our library are preferentially expressed in fetal cochlea. These may play a physiologically important role in the hearing process and represent candidate genes for hereditary hearing impairment.
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PMID:Cloning, characterization, and mRNA expression analysis of novel human fetal cochlear cDNAs. 1367 28

Atp2b2 encodes the plasma membrane Ca(2+)-ATPase type 2 (PMCA2) expressed in various tissues, including stereocilia of cochlear and vestibular hair cells, cerebellar Purkinje cells, and lactating mammary epithelia. Mutations of the gene lead to deafness, ataxia, and reduced Ca(2+) levels in milk. Heterozygous mutants also have abnormal hearing, suggesting that precise regulation of Atp2b2 is required for normal function. In this study, we describe Atp2b2 5'-untranslated region genomic structure and transcript usage in mice. Using 5'-rapid amplification of cDNA ends, we observed four transcripts: types alpha, beta, mu and delta, each splicing into a common ATG-containing exon. Types alpha and beta correspond to previously published mammalian cDNA sequences. Types mu and delta constitute novel 5'-untranslated region sequences, and were observed at high levels only in lactating mammary gland. Using real-time reverse transcriptase polymerase chain reaction, we quantified relative transcript usage across several tissues. We show that alpha and beta are abundant throughout the CNS, as well as the cochlea. When we microdissected the cochlea into hair cell and spiral ganglion containing fractions, we found that cochlear hair cell expression is mediated through the type alpha transcript. In situ hybridization studies in cerebellum using exon-specific probes revealed that alpha dominates in Purkinje neurons, while beta is enriched in cerebellar granule neurons. We compared 5'-untranslated region sequence across multiple species, and found high conservation around the first exons for alpha and beta in mammals, but not other species. The regions around the mu and delta first exons are highly conserved between rat and mouse, but less so with other species. Our results show that expression of Atp2b2 is highly regulated, using four different transcriptional start regions, two of which are differentially expressed in neuronal tissue. This suggests that unique regulatory mechanisms are used to control Atp2b2 expression in different types of cells.
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PMID:Atp2b2, encoding plasma membrane Ca2+-ATPase type 2, (PMCA2) exhibits tissue-specific first exon usage in hair cells, neurons, and mammary glands of mice. 1667 32

Nerve growth factors play key roles in spiral ganglion cells survival and excitability. Our aim was to determine gene expression patterns of glial cell line-derived neurotrophic factor family (GDNF) members and their receptors in the auditory nerve and inferior colliculus of deafened rats. The gene expression of GDNF, persephin, artemin and neurturin, and their receptors GFRalpha1, GFRalpha2, GFRalpha3 and Ret, was determined by semiquantitative reverse transcriptase-polymerase chain reaction using GAPDH expression as an internal standard. Following deafness, no significant changes in expression of GDNF family genes were found in inferior colliculus. In contrast, artemin, GDNF, GFRalpha1-3 and Ret RNA expression were strongly upregulated in the auditory nerve following deafness, indicating their importance in protecting the auditory nerve against cell damage.
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PMID:Upregulation of glial cell line-derived neurotrophic factor and artemin mRNA in the auditory nerve of deafened rats. 1673 79

After a yeast two-hybrid screen identified prosaposin as a potential interacting protein with the nicotinic acetylcholine receptor (nAChR) subunit alpha10, studies were performed to characterize prosaposin in the normal rodent inner ear. Prosaposin demonstrates diffuse organ of Corti expression at birth, with gradual localization to the inner hair cells (IHCs) and its supporting cells, inner pillar cells, and synaptic region of the outer hair cells (OHCs) and Deiters' cells (DCs) by postnatal day 21 (P21). Microdissected OHC and DC quantitative reverse transcriptase-PCR and immunohistology localizes prosaposin mRNA to DCs and OHCs, and protein predominantly to the apex of the DCs. Subsequent studies in a prosaposin knock-out (KO) (-/-) mouse showed intact but slightly reduced hearing through P19, but deafness by P25 and reduced distortion product otoacoustic emissions from P15 onward. Beginning at P12, the prosaposin KO mice showed histologic organ of Corti changes including cellular hypertrophy in the region of the IHC and greater epithelial ridge, a loss of OHCs from cochlear apex, and vacuolization of OHCs. Immunofluorescence revealed exuberant overgrowth of auditory afferent neurites in the region of the IHCs and proliferation of auditory efferent neurites in the region of the tunnel of Corti. IHC recordings from these KO mice showed normal I-V curves and responses to applied acetylcholine. Together, these results suggest that prosaposin helps maintain normal innervation patterns to the organ of Corti. Furthermore, prosaposin's overlapping developmental expression pattern and binding capacity toward the nAChR alpha10 suggest that alpha10 may also play a role in this function.
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PMID:Progressive deafness and altered cochlear innervation in knock-out mice lacking prosaposin. 1716 97

Rubella is generally a mild and self-limited disease in children. During pregnancy, rubella can have potentially devastating effects on the developing fetus. Postnatal rubella is transmitted primarily by inhalation of virus-laden airborne droplets or direct contact with infected nasopharyngeal secretions. In susceptible pregnant women, the virus may cross the placenta and spread through the vascular system of the developing fetus. Postnatally acquired rubella typically begins with fever and lymphadenopathy, followed by an erythematous, maculopapular rash. The rash classically begins on the face, spreads cephalocaudally, becomes generalised within 24 hours, and disappears within 3 days. Maternal rubella, especially during early pregnancy, may lead to miscarriage, intrauterine fetal death, premature labour, intrauterine growth retardation, and congenital rubella syndrome. Cataracts, congenital heart defects, and sensorineural deafness are the classic triad of congenital rubella syndrome and they typically occur if the fetal infection occurs in the first 11 weeks of gestation. Laboratory confirmation of rubella virus infection can be based on a positive serological test for rubella-specific immunoglobulin M antibody; a four-fold or greater increase in rubella-specific immunoglobulin G titres between acute and convalescent sera; or detection of rubella virus RNA by reverse transcriptase-polymerase chain reaction. Treatment is mainly symptomatic. Universal childhood immunisation and vaccination of all susceptible patients with rubella vaccine to decrease circulation of the virus are cornerstones to prevention of rubella and, more importantly, congenital rubella syndrome.
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PMID:Rubella (German measles) revisited. 3096 19