Engineering hypoallergenic cats: Mutations found in South African cats suggest allergen expression may not be essential

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Regression analysis of Fel d 1 across the Felidae lineages. The Fel d 1 sequences and orthologs from domestic and exotic cats were aligned with the GenBank DNA or protein references for Fel d 1. A) The exotic cat species analyzed, representing the eight lineages of Felidae. B) Simple linear regression of the mean pairwise identities (mean ± SEM; %) of the Felidae lineages (N = 1–54 cats per lineage) and modern domestic cats (N = 140 cats) over the approximate evolutionary timeline of the cat family (36). R2 values: 0.93, 0.82, 0.57, and 0.51 for CH1 DNA (orange), chain 1 protein (yellow), CH2 DNA (green), and chain 2 protein (blue), respectively. Credit: PNAS Nexus (2024). DOI: 10.1093/pnasnexus/pgae447

Gene editing could create hypoallergenic cats, according to a sequence analysis of the protein that triggers allergies to cats. Some 15% of people are allergic to cats, and symptoms can be severe. Martin D. Chapman and colleagues investigated CH1 and CH2, genes that code for the allergen, Fel d 1. The work is published in the journal PNAS Nexus.

Cats produce Fel d 1 in their sebaceous, salivary, perianal, and lachrymal glands. The function of Fel d 1 is unknown but comparisons of Fel d 1 sequences and homologs from 276 domestic or exotic cats—including cougars, cheetahs, lions, tigers, and jaguars, among others—suggests that CH1 and CH2 have been under active selection, and thus potentially confer some fitness advantage.

Fel d 1 may be involved in immune regulation, skin protection, or chemical communication among cats. However, cats genetically modified to lack CH2 seem healthy and low levels of conserved sequences between species suggest that the allergen is either nonessential or that the function of Fel d 1 varies among cat species.

Two of the analyzed cats—a cougar and a black-footed cat, a small wildcat from Southern Africa—had mutations that likely prevented Fel d 1 expression, further indicating that the allergen may not be essential for cats. According to the authors, using CRISPR technology to delete CH1 and CH2 could create hypoallergenic cats.

More information: Clifford W Cleveland et al, Genetic diversity of the major cat allergen, Fel d 1, PNAS Nexus (2024). DOI: 10.1093/pnasnexus/pgae447

Journal information: PNAS Nexus

Provided by PNAS Nexus