| First Author | Ferguson SM | Year | 2004 |
| Journal | Proc Natl Acad Sci U S A | Volume | 101 |
| Issue | 23 | Pages | 8762-7 |
| PubMed ID | 15173594 | Mgi Jnum | J:90846 |
| Mgi Id | MGI:3044863 | Doi | 10.1073/pnas.0401667101 |
| Citation | Ferguson SM, et al. (2004) Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice. Proc Natl Acad Sci U S A 101(23):8762-7 |
| abstractText | Presynaptic acetylcholine (ACh) synthesis and release is thought to be sustained by a hemicholinium-3-sensitive choline transporter (CHT). We disrupted the murine CHT gene and examined CHT-/- and +/- animals for evidence of impaired cholinergic neurotransmission. Although morphologically normal at birth, CHT-/- mice become immobile, breathe irregularly, appear cyanotic, and die within an hour. Hemicholinium-3-sensitive choline uptake and subsequent ACh synthesis are specifically lost in CHT-/- mouse brains. Moreover, we observe a time-dependent loss of spontaneous and evoked responses at CHT-/- neuromuscular junctions. Consistent with deficits in synaptic ACh availability, we also observe developmental alterations in neuromuscular junction morphology reminiscent of changes in mutants lacking ACh synthesis. Adult CHT+/- mice overcome reductions in CHT protein levels and sustain choline uptake activity at wild-type levels through posttranslational mechanisms. Our results demonstrate that CHT is an essential and regulated presynaptic component of cholinergic signaling and indicate that CHT warrants consideration as a candidate gene for disorders characterized by cholinergic hypofunction. |
