2018 Targeting Trends Review

Amano M, Amiya N, Yamamoto N, Osugi T, Tsutsui K (2019) Immunohistochemical detection of prolactin-releasing peptide2 in the brain of the inshore hagfish Eptatretus burgeri. Gen Comp Endocrinol 274:1-7. doi: 10.1016/j.ygcen.2018.12.005

Objective: To identify Prolactin-releasing peptide2 (PrRP2) in hagfish.

Summary: The study demonstrates, for the first time, that PrRP2 is expressed in the brain of inshore hagfish. The restricted distribution of PrRP2-ir fibers in the HYinf suggests that PrRP2 does not directly regulate the pituitary gland, but regulates the function of the HYinf where PQRFa and CRH are expressed.

Usage: Immunohistochemistry (1:1000). The authors clarified the cross-reactivity of the antibody against other CRH family peptides, such as urocortin-I, II, III, urotensin-I, and sauvagine: the cross-reactivity of anti-CRH against CRH family peptides was found to be less than 0.01%, indicating the specificity of the antibody.

Related Products: Corticotropin Releasing Hormone Rabbit Polyclonal (Cat. #AB-02)

Chew C, Kiley B, Sengelaub D (2019) Neuroprotective effects on the morphology of somatic motoneurons following the death of neighboring motoneurons: A role for microglia. Dev Neurobiol 79:131-154. doi: 10.1002/dneu.22652

Related Products: CTB-SAP (Cat. #IT-14)

Gao ZR, Chen WZ, Liu MZ, Chen XJ, Wan L, Zhang XY, Yuan L, Lin JK, Wang M, Zhou L, Xu XH, Sun YG (2019) Tac1-expressing neurons in the periaqueductal gray facilitate the itch-scratching cycle via descending regulation. Neuron 101(1):45-59.e9. doi: 10.1016/j.neuron.2018.11.010

Objective: To determine the neural mechanism promoting the itch-scratching cycle.

Summary: Ablation of Tac1+ but not SST+ neurons decreases itch-induced scratching behavior. l/vlPAG Tac1+ neurons Induce Scratching Behavior via a Descending Pathway.

Usage: To ablate the spinal GRPR+ neurons, mice were intrathecally injected with Bombesin-SAP or Control Blank-SAP (400 ng/5 mL).

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Quattrochi LE, Stabio ME, Kim I, Ilardi MC, Michelle Fogerson P, Leyrer ML, Berson DM (2019) The M6 cell: A small-field bistratified photosensitive retinal ganglion cell. J Comp Neurol 527(1):297-311. doi: 10.1002/cne.24556

Summary: M6 cells express low levels of melanopsin and have correspondingly weak intrinsic light responses.

Usage: In all experiments involving melanopsin immunofluorescence, melanopsin immunodetection was enhanced using tyramide signal amplification coupled with horseradish peroxidase (HRP)-paired with goat anti-rabbit IgG and an Alexa fluorophore. 1:10,000.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Dhande OS, Seabrook TA, Phan AH, Salaly LD, Ishiko N, Nguyen PL, Wang JT, Evans SM, Huberman AD (2018) Assembly of functionally antagonistic visual circuits for controlling pupil dynamics. bioRxiv 500868. doi: 10.1101/500868

Objective: Investigate the mechanisms controlling the specification and establishment of parallel sensory pathways.

Summary: Identification of a novel genetic program that marks and is required for the development of non-image-forming parallel visual pathways.

Usage: Immunohistochemistry (1:1000)

Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)

Berhani O, Glasner A, Kahlon S, Duev-Cohen A, Yamin R, Horwitz E, Enk J, Moshel O, Varvak A, Porgador A, Jonjic S, Mandelboim O. (2019) Human anti-NKp46 antibody for studies of NKp46-dependent NK cell function and its applications for type 1 diabetes and cancer research. Eur J Immunol 49(2):228-241. doi: 10.1002/eji.201847611

Objective: To investigate human NKp46 activity and its critical role in Natural Killer (NK) cell biology.

Summary: A unique anti-human NKp46 monoclocal antibody was developed and conjugated to Saporin. Targeted toxin inhibits growth of NKp46-positive cells; thus, exemplifying the potential as an immunotherapeutic drug to treat NKp46-dependent diseases, such as, type I diabetes and NK and T cell related malignancies.

Usage: Conjugation of the antibodies to Saporin, treatment of cells, and cell viability assay Biotin-Z Kit instructions.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Kinneer K, Meekin J, Tiberghien AC, Tai YT, Phipps S, Kiefer CM, Rebelatto MC, Dimasi N, Moriarty A, Papadopoulos KP, Sridhar S, Gregson SJ, Wick MJ, Masterson L, Anderson KC, Herbst R, Howard PW, Tice DA (2018) SLC46A3 as a potential predictive biomarker for antibody-drug conjugates bearing noncleavable linked maytansinoid and pyrrolobenzodiazepine warheads. Clin Cancer Res 24(24):6570-6582. doi: 10.1158/1078-0432.CCR-18-1300

Objective: To develop biomarkers to uncover the underlying mechanism of resistance by certain cell lines for ADCs.

Summary: Loss of SLC46A3 expression was found to be a mechanism of innate and acquired resistance to ADCs bearing DM1 and SG3376.

Usage: For Lysosomal trafficking, ADCs were labeled with Fab-pHast human (Cat. #PH-01). Cells were incubated with 3 mg/mL of labeled ADCs at 37°C for desired time points and fluorescence quantified by flow cytometry.

Related Products: Fab-pHast human (Cat. #PH-01)

Cops J, Mullens W, Verbrugge FH, Swennen Q, De Moor B (2018) Selective abdominal venous congestion induces adverse renal and hepatic morphological and functional alterations despite a preserved cardiac function. Sci Rep 8:17757. doi: 10.1038/s41598-018-36189-3

Objective: The consequences of isolated abdominal venous congestion on morphology and function of the kidneys, liver and heart were studied in a rat model.

Summary: This study provides relevant insight in the pathophysiology of abdominal congestion on organ function.

Usage: Western blot. PVDF membrane was incubated overnight at 4 °C in the presence of antibody (1/2000).

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)

Lelieveldt LPWM, Kristyanto H, Pruijn GJM, Scherer HU, Toes REM, Bonger KM (2018) Sequential prodrug strategy to target and eliminate ACPA-selective autoreactive B cells. Mol Pharm 15(12):5565-5573. doi: 10.1021/acs.molpharmaceut.8b00741

Objective: To develop a method to target and selectively eliminate autoreactive B cells using a sequential antigen prodrug targeting strategy.

Summary: The selectivity of the antigen and the possibility to block binding toward circulation ACPA brings us a step closer to the specific elimination of autoreactive B cells for the treatment of patients with ACPA-positive RA.

Usage: Biotinylated CCP1, CArgP1, and CCP1(CNBz) were conjugated with Streptavidin-ZAP in a 4:1 ratio to make peptide-drug conjugates.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Xiong L, Liu Y, Zhou M, Wang G, Quan D, Shen C, Shuai W, Kong B, Huang C, Huang H (2018) Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction. Europace 20(12):2036-2044. doi: 10.1093/europace/euy090

Objective: To evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI).

Summary: Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Usage: 20 μl of CTB-SAP (1.2 mg/ml) was mixed with 4 μl of 3% Evans blue dye to make it visible (CTB-SAP is colorless), ensuring localization within the ganglia. The CTB-SAP/ Evan blue dye solution was slowly and intermittently injected into the left stellate ganglia using a glass micropipette.

Related Products: CTB-SAP (Cat. #IT-14)

Palchaudhuri R, Hyzy SL, Proctor JL, Adams HL, Pearse BR, Sarma G, Aslanian S, Gillard G, Lamothe TL, Burenkova O, Brooks ML, Gabros AD, McDonagh CF, Boitano AE, Cooke MP (2018) Antibody drug conjugates targeted to CD45 or CD117 enable allogeneic hematopoietic stem cell transplantation in animal models. Blood 132:3324. doi: 10.1182/blood-2018-99-119432

Objective: To further investigate and develop the utility of CD45-SAP and CD117-SAP, in combination with immunosuppression, in murine transplant models using i.v. administration in an allogeneic minor mismatch transplant model (Balb/c donor into DBA/2 recipients).

Summary: CD45-SAP or CD117-SAP in combination with immunosuppressants (30Fll and post-transplant Cytoxan) enabled >85% peripheral donor chimerism at 12 weeks post-transplantation. CD45-SAP and CD117-SAP were more effective at conditioning versus 2Gy TBI or pretransplant Cytoxan.

Usage: CD45-SAP (1.9 mg/kg, iv) and CD117-SAP (1mg/kg, iv) in an allogeneic minor mismatch transplant model (Balb/c donor into DBA/2 recipients).

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Ostrin LA, Strang CE, Chang K, Jnawali A, Hung L-F, Arumugam B, Frishman LJ, Smith EL, Gamlin PD (2018) Immunotoxin-induced ablation of the intrinsically photosensitive retinal ganglion cells in rhesus monkeys. Front Neurol 9:1000. doi: 10.3389/fneur.2018.01000

Objective: To develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.

Summary: Findings demonstrated that Melanopsin-SAP was specific for ipRGCs, and induced a graded reduction in the PLR (pupillary light reflex), as well as in ipRGC-driven pupil response with concentration.

Usage: Solutions of 0.316, 1, 3.16, 10, and 50 μg delivered intravitreally.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Bailey D, Catron M, Kovtun O, Macdonald R, Zhang Q, Rosenthal S (2018) Single quantum dot tracking reveals serotonin transporter diffusion dynamics are correlated with cholesterol-sensitive threonine 276 phosphorylation status in primary midbrain neurons. ACS Chem Neurosci 9:2534-2541. doi: 10.1021/acschemneuro.8b00214

Objective: Visualizing SERT behavior at the single molecule level in endogenous systems remains a challenge. The authors utilize quantum dot (QD) single particle tracking (SPT) to capture SERT dynamics in primary rat midbrain neurons.

Summary: Results provide new insights into endogenous neuronal SERT mobility and its associations with membrane cholesterol and SERT phosphorylation status.

Usage: Live Cell QD Tracking – Cells were incubated with 5 μg/mL primary SERT antibody in warm fluorescent media at 37 °C and 5% CO2 for 6 min.

Related Products: SERT Mouse Monoclonal (Cat. #AB-N40)

Qiu M, Li J, Tan L, Zhang M, Zhou G, Zeng T, Li A (2018) Targeted ablation of distal cerebrospinal fluid-contacting nucleus alleviates renal fibrosis in chronic kidney disease. Front Physiol 9:1640. doi: 10.3389/fphys.2018.01640

Objective: To test the hypothesis that distal cerebrospinal fluid-contacting nucleus (dCSF-CNs) might affect the renin-angiotensin system (RAS) in kidney injury progression.

Summary: Less CTB-labeled neurons were found in dCSF-CNs of CTB-SAP-treated rats. Meanwhile, CTB-SAP downregulated AGT, Ang II, AT1R, NOX2, catalase, MCP-1, IL-6, fibronectin, and collagen I, and upregulated ACE2 and Mas receptor. Targeted dCSF-CNs ablation could alleviate renal inflammation and fibrosis in chronic kidney injury.

Usage: CTB-SAP (500 ng) into the lateral ventricles over a 3-min period.

Related Products: CTB-SAP (Cat. #IT-14)

Shibata S, Hayashi R, Okubo T, Kudo Y, Katayama T, Ishikawa Y, Toga J, Yagi E, Honma Y, Quantock AJ, Sekiguchi K, Nishida K (2018) Selective laminin-directed differentiation of human induced pluripotent stem cells into distinct ocular lineages. Cell Rep 25:1668-1679. doi: 10.1016/j.celrep.2018.10.032

Usage: Immunostaining, flow cytometry

Related Products: NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

Ueda H, Neyama H, Nagai J, Matsushita Y, Tsukahara T, Tsukahara R (2018) Involvement of lysophosphatidic acid-induced astrocyte activation underlying the maintenance of partial sciatic nerve injury-induced neuropathic pain. Pain 159:2170-2178. doi: 10.1097/j.pain.0000000000001316

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Zoccal DB, Silva JN, Barnett WH, Lemes EV, Falquetto B, Colombari E, Molkov YI, Moreira TS, Takakura AC (2018) Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. Am J Physiol Lung Cell Mol Physiol 315(5):L891-L909. doi: 10.1152/ajplung.00011.2018

Objective: To investigate the microcircuitry responsible for the distribution of the excitatory signals to the the parafacial respiratory group (pFRG) and the the respiratory central pattern generator (rCPG) in conditions of high CO2.

Summary: The activation of the pFRG late-E neurons during hypercapnia require glutamatergic inputs from the RTN neurons that intrinsically detect changes in CO2/pH.

Usage: Bilateral injections of SSP-SAP (0.6 ng in 100 nL of saline per side).

Related Products: SSP-SAP (Cat. #IT-11)

Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ (2019) Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice. Mol Neurobiol 56(7):4639-4652. doi: 10.1007/s12035-018-1404-2

Objective: To investigate the contribution of CBF neuronal p75NTR to the progression of Alzheimer’s Disease

Summary: Data indicate that a direct interaction between CBF-expressed p75NTR and Aβ does not contribute significantly to the regulation of Aβ load.

Usage: To lesion CBF neurons, a single infusion of mu p75-SAP or control Rabbit IgG-SAP (0.4 mg/ml) was stereotaxically-injected into the basal forebrain.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Garrett AM, Khalil A, Walton DO, Burgess RW (2018) DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proc Natl Acad Sci U S A 115:E10216-E10224. doi: 10.1073/pnas.1809430115

Summary: Focus on DSCAM (Down syndrome cell adhesion molecule 1) self-avoidance function in the mouse retina. DSCAM and members of the cadherin superfamily have also emerged as key contributors to a variety of neurodevelopmental disorders, including autism, schizophrenia, bipolar disease, Down syndrome and intellectual disability.

Related Products: Melanopsin-SAP (Cat. #IT-44)

Han W, Tellez LA, Perkins MH, Perez IO, Qu T, Ferreira J, Ferreira TL, Quinn D, Liu Z-W, Gao X-B, Kaelberer MM, Bohórquez DV, Shammah-Lagnado SJ, de Lartigue G, de Araujo IE (2018) A neural circuit for gut-induced reward. Cell 175:665-678. doi: 10.1016/j.cell.2018.08.049

Objective: To determine relevant gut-brain neuronal circuitry to motivational and emotional states.

Summary: There is a critical role for the vagal gut-to-brain axis in motivation and reward.

Usage: Injected 0.5 µl of CCK-SAP (250 ng/µl) into the R-NG of VGlut2-ires-Cre mice.

Related Products: CCK-SAP (Cat. #IT-31)