Disease relevance of Gjb1

• Surprisingly, in lung adenomas Cx32 and Cx43 expressions were not detected, although the expression of connexins 26 and 46 was present [1].
• Initial analyses of Cx32/Cx47-double-deficient mice showed that these mice developed an action tremor and died on average at 51 d after birth [2].
• Global ischemia induced a selective increase in Cx32 and Cx36 but not Cx43 protein abundance in CA1 before onset of neuronal death, as assessed by Western blot analysis [3].
• Macrophage-related demyelination in peripheral nerves of mice deficient in the gap junction protein connexin 32 [4].
• To explore the role of gap junctional communication in acinar cell response to injury, we analyzed the course of acute pancreatitis induced by injection of cerulein in mice deficient for Cx32, the major gap junction protein expressed in the exocrine pancreas [5].

High impact information on Gjb1

• Severe acute pancreatitis and reduced acinar cell apoptosis in the exocrine pancreas of mice deficient for the Cx32 gene [5].
• Interestingly, chemicals known to induce apoptosis in vivo had no effect on Cx32-deficient pancreatic acinar cells [5].
• Pancreatic acinar cells from Cx32 (-/-) mice failed to express Cx32 as evidenced by reverse transcription-PCR and immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in the number and size of gap junctions [6].
• Although wild-type and Cx32 (-/-) acini were similarly stimulated to release amylase by carbamylcholine, Cx32 (-/-) acini showed a twofold increase of their basal secretion [6].
• On the other hand, propidium iodide and ethidium bromide penetrate very poorly or not at all through Cx31 and Cx32 channels, respectively, but pass through channels of other connexins [7].

Chemical compound and disease context of Gjb1

• Under conditions of hepatic acute-phase response, Cx32 transcripts were not detected in LPS-treated livers of wild-type mice [8].

Biological context of Gjb1

• In order to exclude cross reactions of the corresponding antibodies, retinae from targeted connexin-deficient mice (Cx31 -/-, Cx32 -/- and Cx40 -/-) were used as negative controls for immunoblot and immunofluorescence analyses of wild-type retina [9].
• The expression of Cx26 and Cx32 is induced during pregnancy and lactation, respectively, thus suggesting unique roles for them in the functional development of the gland [10].
• Although none of the truncated connexins affected proliferation rate, the truncated Cx32 and Cx43 proteins suppressed anchorage-independent cell growth in soft agar [11].
• G-6-Pase-positive lesions were strongly promoted by Wy-14,643, both in Cx32-wild-type and Cx32-null mice without significant difference in response between mice of the two genotypes [12].
• Connexin-47 and connexin-32 in gap junctions of oligodendrocyte somata, myelin sheaths, paranodal loops and Schmidt-Lanterman incisures: implications for ionic homeostasis and potassium siphoning [13].

Anatomical context of Gjb1

• Expression profiles of the connexin genes, Gjb1 and Gjb3, in the developing mouse cochlea [14].
• A transitory expression of Gjb1 was found in the basal and intermediate cells of the stria vascularis [14].
• In the developing otocyst epithelium, some restricted domains expressed Gjb3 and Gjb1 whilst high levels of both transcripts were present in the surrounding mesenchymal tissue [14].
• Gjb3 and Gjb1 expression was spatiotemporally modulated within the sensory hair cells and the various supporting cells that compose the developing organ of Corti [14].
• These results indicate that Cx32 formation and/or Cx32-mediated intercellular communication may participate in the formation of functional tight junctions and actin organization [15].

Associations of Gjb1 with chemical compounds

• We recently demonstrated that liver tumourigenesis is accelerated in Cx32-wild-type but not in Cx32-null mice by the model tumour promoter phenobarbital (PB) [12].
• In the present study, male Cx32-wild-type and Cx32-null mice were treated with a single injection of 90 micro g/g body wt of N-nitrosodiethylamine (DEN) at 6 weeks of age and were subsequently kept on a diet containing the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) or on control diet [12].
• The antigenic site for alpha Cx32/26-E2 was only accessible after exposure of the extracellular face by separation of the junctional membranes in 8 M urea, pH 12 [16].
• These results may indicate a role of Cx32 and Cx43 in urethane-induced lung carcinogenesis, since their absence may contribute to the development of urethane induced lung tumors [1].
• Stimulated fluid production by the glands from Cx32-deficient mice was abnormally low in female glands compared with controls at low topical doses of carbachol [17].

Physical interactions of Gjb1

• The promoter region of the mouse Cx32 gene contains two putative binding sites for the transcription factor HNF-1 and consensus motifs for NF-1 as well as NFkappaB within 680 bp upstream of the main transcription start site [18].

Regulatory relationships of Gjb1

• Tight junction protein MAGI-1 is up-regulated by transfection with connexin 32 in an immortalized mouse hepatic cell line: cDNA microarray analysis [19].
• Additional studies testing Mist1 gene constructs in pancreatic exocrine cells confirmed that Mist1 transcriptionally regulates expression of the Cx32 gene [20].
• Western blot analysis of Cx26 showed that female Cx32-deficient mice expressed Cx26 [17].
• Cx29 expressed in N2A cells did not induce intercellular conductances but did participate in the formation of active channels when coexpressed with Cx32 [21].
• Connexin 32 gap junctions enhance stimulation of glucose output by glucagon and noradrenaline in mouse liver [22].

Other interactions of Gjb1

• In transient wild-type Cx32 transfectants, immunocytochemistry revealed that endogenous occludin was in part localized at cell borders, where it was colocalized with Cx32, whereas neither was detected in parental cells [15].
• In mature myelin-forming Schwann cells, expression of multiple connexins, i.e. connexin (Cx) 43, Cx29, Cx32, and Cx46 (after nerve injury) has been detected [23].
• By freeze-fracture replica immunogold labeling, large gap junctions between oligodendrocyte somata and astrocyte processes contained much more connexin 47 than connexin 32 [13].
• In the adult cochlea Gjb1 transcripts disappeared while Gjb3 expression remained present in fibrocytes with specific expression patterns [14].
• The map extends from the Gjb-1 locus to the Xist locus and demonstrates the order of probes inseparable by genetic analysis [24].

Analytical, diagnostic and therapeutic context of Gjb1

• High expression of MAGI-1 in Cx32 transfectants was confirmed by Western blotting and RT-PCR [19].
• Transcripts of both connexin32 (Cx32) and connexin43 (Cx43) were detected by RT-PCR in both components of the COC [25].
• Studies with such mice indicate that Cx32 plays a key role in liver regeneration after partial hepatectomy [26].
• We show that Cx32-deficient mice develop a late-onset progressive peripheral neuropathy with abnormalities comparable to those associated with CMTX, thus providing proof of the critical role of Cx32 in the maintenance of peripheral nerve myelin and an animal model for CMTX [27].
• Furthermore, intraperitoneal injection, two weeks after birth, of the carcinogen diethylnitrosamine (DEN) led, after one year, both to more liver tumors in Cx32-deficient mice than in controls, and to accelerated tumor growth [28].

References