Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle.

Mathew D Littlejohn,Kathryn Tiplady,Thomas Johnson,Chad Harland,Dorian J Garrick,Wanbo Li,Kristen M Henty,Russell G Snell,Stephen R Davis,Richard J Spelman,Bruce C Shanks,Thomas Lopdell,Steven D Lukefahr,Richard G Sherlock

doi:10.1038/ncomms6861

Abstract

Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation.

Highlights

Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species
Lactation shares some common biology with these processes, where similarities in the structure and function of mammary, sweat and sebaceous glands has led to the hypothesis that mammary glands evolved from a pilosebaceous apocrine structure in the skin[1]
The literature describing the cellular and molecular physiology of each of these phenomena is vast, and in the case of mammary and hair follicle biology, these processes are known to be broadly regulated by a range of hormones including oestrogen[2,3,4], testosterone[4,5,6], growth hormone[7,8], prolactin[9,10] and others[11]

Summary

Results

A novel pleiotropic syndrome in dairy cattle. Heart rates were not significantly different between groups (two-sided t-test, P 1⁄4 0.149; Supplementary Fig. 2); respiration rates were approximately four times greater in affected individuals (two-sided t-test, P 1⁄4 2.6 Â 10 À 14; Fig. 1d). These effects were reproducible over multiple time points and days (Supplementary Table 1 and Supplementary Fig. 2). Since this heat stress response could have been partly attributable to increased hair length, five of twelve affected

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Discussion

Methods