References

Garaudé S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, Dell’ Aglio A, Juskevicius D, Zuin J, Burgold T, Wang S, Katta V, Manquen G, Li Y, Larrue C, Camus A, Durzynska I, Wellinger LC, Kirby I, Van Berkel PH, Kunz C, Tamburini J, Bertoni F, Widmer CC, Tsai SQ, Simonetta F, Urlinger S, Jeker LT (2024) Selective haematological cancer eradication with preserved haematopoiesis. Nature 630(8017):728-735. doi: 10.1038/s41586-024-07456-3 PMID: 38778101

Objective: To demonstrate that an antibody–drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specifc depletion of the entire haematopoietic system, including Haematopoietic stem cells ( HSC).

Summary: Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type.

Usage: For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody (BC8 or MIRG451 mAbs) and saporin–streptavidin (IT-27) at a 1:1 molar ratio for 30 min at room temperature

Related Products: Anti-CD45.2-SAP (Cat. #IT-91), Streptavidin-ZAP (Cat. #IT-27)

Barioni NO, Beduschi RS, da Silva AV, Martins MG, Almeida-Francia CCD, Rodrigues SA, López DE, Gómez-Nieto R, Horta-Júnior JAC (2024) The role of the ventral nucleus of the trapezoid body in the auditory prepulse inhibition of the acoustic startle reflex. Hearing Research doi: 10.1016/j.heares.2024.109070 PMID: 38972084

Objective: To study the acoustic startle response through elimination of the ventral nucleus of the trapezoid body neurons via Anti-ChAT-SAP injection.

Summary: The elimination of ventral nucleus of the trapezoid body (VNTB) is used while measuring the auditory prepulse inhibition and acoustic startle response with and without this group of neurons to study their role in rats. It was found The VNTB stands as the sole identified source of cholinergic inputs to Cochlear root neurons.

Usage: Lesions in the VNTB were performed via a bilateral microinjection of a neurotoxin selective for cholinergic neurons, the anti-ChAT-saporin (IT-42, 0.25 ug/μl, 400 nL)

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Simpson J, Starke CE, Ortiz AM, Ransier A, Darko S, Llewellyn-Lacey S, Fennessey CM, Keele BF, Douek DC, Price DA, Brenchley JM (2024) Immunotoxin-mediated depletion of Gag-specific CD8+ T cells undermines natural control of Simian immunodeficiency virus. JCI Insight e174168. doi: 10.1172/jci.insight.174168 PMID: 38885329

Objective: To investigate the role of gag epitope-specific CD8+ T cells in the immune control of Simian Immunodeficiency Virus (SIV) in a nonhuman primate model.

Summary: Antibody-mediated depletion studies suggest that CD8+ T cells suppress SIV replication, but bulk depletion of CD8+ T cells may increase SIV target cells. Authors selectively depleted CD8+ T cells specific to the CM9 epitope, but this didn’t suppress viral replication in SIV-infected rhesus macaques. The data indicate that CM9-specific CD8+ T cells alone are not sufficient for immune control of SIV.

Usage: Streptavidin-ZAP was added stepwise to purified CM9 monomers to a final molar ratio of 1:4 and administered intravenously at a doses of 350 pmol/kg, 500 pmol/kg, 1 nmol/kg, or 2 nmol/kg at various time intervals.

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

See Also:

• Hess PR et al. Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-3307, 2007.
• Leitman EM et al. Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities. PLoS One. 2017;12(10):e0184496.

Nishioka M, Hata T (2024) Cholinergic interneurons in the dorsal striatum play an important role in the acquisition of duration memory. Eur J Neurosci 59(11):3061-3073. doi: 10.1111/ejn.16337 PMID: 38576223

Objective: To investigate duration-memory formation in the dorsal striatum.

Summary: Rats were sufficiently trained using a peak-interval 20s procedure and then infused with anti-choline acetyltransferase–saporin into the dorsal striatum to cause selective ablation of cholinergic interneurons. Lesions of the cholinergic cells show delayed memory acquisition and suggest dorsal striatum neurons play a role in new duration memory.

Usage: Each group of rats received aCSF or anti-choline acetyltransferase (ChAT)–saporin (Anti-ChAT-SAP, IT-42) at 0.5 μg/μL at 0.5 μl/min for 2 mins.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Nirogi R, Jayarajan P, Benade V, Abraham R, Goyal VK (2024) Hits and misses with animal models of narcolepsy and the implications for drug discovery. Expert Opin Drug Discov 19(6):755-768. doi: 10.1080/17460441.2024.2354293 PMID: 38747534

Objective: To review the usage of Orexin-B-SAP treated rats in the development of drug candidates for the treatment of narcolepsy.

Summary: Examines pharmacological agents used for the modeling of narcolepsy in animals and contrasts it with narcolepsy expression in real patients. Additionally summarizes the discovery of the orexin system in narcolepsy and how animal models aided in that discovery.

Usage: Orexin- B-saporin (IT-20) was injected into the lateral hypothalamus of rats.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Yang Q, Liu L, He F, Zhao W, Chen Z, Wu X, Rao B, Lin X, Mao F, Qu J, Zhang J (2024) Retinal ganglion cell type-specific expression of synuclein family members revealed by scRNA-sequencing. Int J Med Sci 21(8):1472-1490. doi: 10.7150/ijms.95598

Objective: To analyze the single-cell transcriptome in healthy and injured retinas to investigate their expression patterns and roles.

Summary: The study revealed that Snca expression varies across RGC subtypes, while Sncb and Sncg are uniformly expressed. Following traumatic axonal injury, Snca, Sncb, and Sncg levels decreased. The proportions of α-Syn-positive RGCs and ipRGCs remained unchanged, with notable changes in Ptn-Ncl and NCAM signaling pathways preceding cell death.

Usage: Immunofluorescence staining (AB-N39) (1:3000).

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

Loften A (2024) Cholinergic modulation of dopamine-related effects of ethanol in the rat. Univ Gothenburg Thesis.

Objective: To explore the role of acetylcholine and cholinergic interneurons (CIN) in ethanol-induced dopamine (DA) release and in the reinforcing effects of ethanol.

Summary: The author’s thesis supports an important role of accumbal CIN in ethanol ́s DA releasing and reinforcing effects, opening up for new potential pharmacological targetsfor treatments of alcohol use disorder.

Usage: in vivo rat model with depletion of accumbal CIN was developed utilizing anti-choline acetyltransferase-saporin (IT-42)

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Toledo C, Del Rio R (2024) Cardiorespiratory disturbances in Alzheimer’s disease: A focus on the contribution of sympathetic premotor neurons. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.2540

Objective: To characterize cardiorespiratory function in AD patients and then to determine the role of RVLM-C1 neurons in autonomic and sleep-disordered breathing in APP/PS1 double transgenic mice, and experimental model showing AD-like pathology.

Summary: Results show that RVLM-C1 neurons play a main role in the development/maintenance of cardiorespiratory disorders in experimental AD.

Usage: Bilateral stereotaxic injections of Anti-DBH-SAP (IT-03) into the RVLM were used to selectively destroy C1 neurons.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Janes T, Cardani S, Pagliardini S (2024) The progestinic drug, etonogestrel, rescues breathing in a rodent model of central chemoreflex impairment. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.978

Objective: Assessing the efficacy of etonogestrel as a treatment to congenital hypoventilation syndrome (CCHS).

Summary: Etonogestrel can stimulate breathing and CO2-chemoreflexes and could be used to treat congenital hypoventilation syndrome. A model of CCHS was created in rats through the ablation of retrotrapezoid nucleus neurons with substance-P saporin. In this CCHS model-rat Etonogestrel was assessed for its ability to return breathing back to normal and for its mechanism of action.

Usage: Rats were lesioned with SSP-SAP [IT-11] targeting the retrotrapezoid nucelus (R.V.N.) neurons.

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

Ketabforoush A, Wang M, Smith C, Arnold WD, Nichols N (2024) Longitudinal assessment of outcome measures of diaphragm motor unit connectivity as biomarkers of phrenic motor unit degeneration and compensation. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.1402

Objective: Using CTB-SAP to lesion motor neurons and measuring motor neuron connectivity and cell death, as a model for phrenic motor neuron degeneration.

Summary: Processes such as injury or aging can affect motor neurons and cause degeneration. CTB-SAP is used to mimic this phenomenon and is used to cause motor degeneration in the diaphram of rats. The motor neurons and motor units have plasticity and the ability to compensate for this damage and the authors seek to use the created rat model to measure this motor unit connectivity.

Usage: Rats received bilateral intrapleural injections of 25 μg of CTB-SAP (IT-14) as well as 25 more μg of free CTB. Control mice received 25 μg of free saporin and 25 μg of CTB.

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