p(MGI:Tmem35a)
General characterization showed that the knockout mice as compared to their wild-type littermates show no changes in body weight, have slight increases in body temperature (Figures S3A and S3B), and exhibit significantly enhanced locomotor activity (Figures S2A and S2B) PubMed:28445721
These experiments showed that NACHO is most concentrated in the heavy (P3) and light (P4) microsomal fractions (Figures 3C and 3D), which contain resident endoplasmic reticulum (ER) proteins including calnexin PubMed:28445721
A very recent study also reported memory defects in mice lacking NACHO/TMEM35 done by scientists unaware of NACHO’s role in controlling nAChRs (Kennedy et al., 2016) PubMed:28445721
Importantly, NACHO knockout mice show complete loss of alpha7 ligand binding and channel function indicating that NACHO is required for formation of alpha7 receptors (Gu et al., 2016) PubMed:28445721
These experiments showed that NACHO is most concentrated in the heavy (P3) and light (P4) microsomal fractions (Figures 3C and 3D), which contain resident endoplasmic reticulum (ER) proteins including calnexin PubMed:28445721
We previously showed that [125I]alpha-bungarotoxin binding is absent in NACHO knockout mice brain (Gu et al., 2016), which express normal levels of RIC-3 mRNA (Figure S1B) PubMed:28445721
[125I]epibatidine binding was decreased in all brain regions evaluated—it was reduced by 66% in cortex, 39% in striatum, and 51% in medial vestibular nucleus (MVN) (Figures 5A and 5D) PubMed:28445721
This partial reduction fits with our data showing that NACHO enhances [3H]epibatidine binding to alpha4beta2 and other heteromeric nAChRs but that some [3H]epibatidine binding occurs to certain heteromeric nAChRs in the absence of NACHO (Figure 2B) PubMed:28445721
Labeling of alpha6-containing nAChRs in striatum by [125I]conotoxin MII is virtually abolished in NACHO knockout mice (Figures 5B and 5D), indicating a vital role for NACHO in assembly of these presynaptic receptors PubMed:28445721
Consistent with our previous autoradiographic results (Gu et al., 2016), we found no detectable [3H]alpha-bungarotoxin binding to brain membranes from NACHO knockouts PubMed:28445721
In membranes from cerebral cortex, hippocampus, and striatum, we found that levels of [3H]epibatidine binding sites are decreased by 50%–75% PubMed:28445721
NACHO knockouts did not show changes in levels of [3H]epibatidine binding to membranes from superior cervical ganglia (wild-type [WT] 329.0 ± 17.2, knockout [KO] 322.8 ± 4.0 fmol/mg protein), which primarily express receptors containing alpha3beta4-containing receptors (David et al., 2010) PubMed:28445721
General characterization showed that the knockout mice as compared to their wild-type littermates show no changes in body weight, have slight increases in body temperature (Figures S3A and S3B), and exhibit significantly enhanced locomotor activity (Figures S2A and S2B) PubMed:28445721
The NACHO knockouts showed increased total number of arm entries in the Y-maze, which fits with their enhanced locomotor activity (Figure S2F) PubMed:28445721
General characterization showed that the knockout mice as compared to their wild-type littermates show no changes in body weight, have slight increases in body temperature (Figures S3A and S3B), and exhibit significantly enhanced locomotor activity (Figures S2A and S2B) PubMed:28445721
In the Morris water maze, NACHO knockout mice were delayed in learning the task during acquisition days 1–4 and showed fewer target crossings in the probe test (Figures S2Cand S2D), despite showing no significant difference for genotype on average speed through each acquisition day (ANOVA: F[1,28] = 0.004; p = 0.9492; data not shown) PubMed:28445721
A very recent study also reported memory defects in mice lacking NACHO/TMEM35 done by scientists unaware of NACHO’s role in controlling nAChRs (Kennedy et al., 2016) PubMed:28445721
NACHO knockout mice also showed deficits of spontaneous alternation in the Y-maze compared to wild-type littermates (Figure S2E) PubMed:28445721
NACHO knockout mice also showed deficits of spontaneous alternation in the Y-maze compared to wild-type littermates (Figure S2E) PubMed:28445721
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.