In the study in NZM2410 mice involving the complete knockout of ERα, the ability of the Esr1tm4.2Ksk allele to reduce lupus nephritis was abrogated by ovariectomy and could not be restored by estrogen treatment, leading the authors to conclude that it was disruption of another component of the hypothalamic-pituitary-gonadal axis, possibly testosterone, rather than loss of ERα that reduced nephritis in NZM2410 mice carrying the complete knockout allele of ERα (45). Here, ESR1 is linked to nephritis.