Current status of immunodeficient mouse models as substitutes to reduce cat and dog use in heartworm preclinical research

Dagley, Jessica, DiCosty, Utami, Fricks, Crystal, Mansour, Abdelmoneim, McCall, Scott, McCall, John W, Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476 (2024) 'Current status of immunodeficient mouse models as substitutes to reduce cat and dog use in heartworm preclinical research'. F1000Research, Vol 13, e484.

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Abstract

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2-/-γc-/- mice. We conclude that in addition to NSG and NXG mice, RAG2-/-γc-/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

Item Type:	Article
Subjects:	QX Parasitology > QX 20 Research (General) QX Parasitology > Helminths. Annelida > QX 203 Nematoda W General Medicine. Health Professions > W 20.5 Biomedical research
Repository link:	Item title Item URI Dataset for 'Current status of immunodeficient mouse models as substitutes to reduce cat and dog use in heartworm preclinical research' https://archive.lstmed.ac.uk/id/eprint/24740
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.12688/f1000research.149854.1
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	11 Jun 2024 11:30
Last Modified:	11 Jun 2024 11:45
URI:	https://archive.lstmed.ac.uk/id/eprint/24633

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