The luteinizing hormone receptor (LHCGR), a member of the G protein-coupled receptor family, is essential for fertility in males and females, with implications for studying gonadotropin hormones and receptors in reproductive physiology and pathophysiology, as well as cancer.
The KiLHRD582G knock-in allele has the constitutively-active D582G mutation in exon 11 of the mouse luteinizing hormone/choriogonadotropin receptor locus (Lhcgr); analogous to the most common D578G mutation found in human boys with familial male-limited precocious puberty (FMPP).
The phenotype described below is for mice maintained on a B6129SF1/J genetic background.
Similar to boys with FMPP, heterozygous (KiLHRD582G/+) male mice exhibit precocious puberty (early puberty) by 15 days of age. Leydig cell hyperplasia and elevated testosterone (in the context of prepubertal [low] luteinizing hormone levels) is observed as early as 7 days of age and through adulthood (24 weeks old). In addition, the donating investigator reports that although heterozygous males have normal sperm count/motility, they show progressive infertility and fail to produce litters by ~5-6 months of age. Compared to wildtype males, KiLHRD582G/+ males are more aggressive to other males, but KiLHRD582G/+ males are not aggressive to breeder females.
While human females with the corresponding activating mutation exhibit no phenotypic abnormalities, female KiLHRD582G/+ mice exhibit early puberty (~15 days old), infertility, elevated steroid hormone levels (testosterone, estradiol and progesterone), polycystic ovaries (as early as three weeks of age) and granulosa cell tumors (~50% by six months of age). The donating investigator reports no increased aggression in KiLHRD582G/+ females.
Because of the phenotype, the donating investigator reports it can be difficult to maintain the colony. They use harem mating of a young heterozygous male (starting at seven weeks of age) to three units of B6129SF1/J female pairs; rotating the male to a new female pair every two weeks. It has not been attempted to make this strain homozygous to date (July 2016).
