Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle

Abstract

Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle - Angus and Jersey. Gene-edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene-edited. Moreover, gene-edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.

Keywords: PRLR; cattle; gene editing; slick allele; thermotolerance.

FIGURE 1

Example of differences in phenotype between slick and non‐slick animals. Shown are two Angus bulls. The photograph was taken on August 30, 2022, when animals were 346–422 days old and when animals had short, summer hair coat. Partial image of a third animal to the right of the image has been digitally removed. The animal inheriting the edited version of PRLR (ear tag S013) has a very short hair coat typical of slick animals. This is most easily visualized in the photograph by comparing appearance of the slick animal with the wild‐type animal with ear tag S010. Differences in hair length are most visually noticeable in the region of the face (notice that hair in the poll is largely absent in the slick animal and its facial hair is shorter) and in the neck (notice the appearance of wrinkles in the slick animals which are visible because of the very short hair coat).

FIGURE 2

Differences between slick and non‐slick animals in regulation of body temperature during heat stress (August). Data are least‐squares means ± SEM for vaginal temperature recorded at 15 min intervals in heifers (A), and rectal temperature (B), skin temperature (C), respiration rate (D) measured in the afternoon for bulls and heifers.

FIGURE 3

Differences between slick and non‐slick animals in body weight (A), hair weight (B) and scrotal circumference (C). Data are means ± SEM (A) or least‐squares means ± SEM.

FIGURE 4

Differences between slick and non‐slick animals in carcass characteristics as determined by ultrasound at an average age of 438 days of age for slick and non‐slick animals. Data are least‐squares means ± SEM for longissimus thoracis cross‐sectional area (A), subcutaneous fat thickness over the longissimus thoracis, intramuscular fat percent in longissimus thoracis (C) and subcutaneous fat thickness at the intersection of the biceps femoris and gluteus medius muscles (D). [Correction added 6 August, 2024 after original online publication: In panel B, P = 0.0058 has been corrected to P = 0.058.]

FIGURE 5

Circulating concentrations of plasma prolactin and insulin‐like growth factor 1 (IGF1). Data are least‐squares means ± SEM.