Mouse Genome Informatics
hm
    Kiss1rtm1Coll/Kiss1rtm1Coll
129S6.Cg-Gpr54tm1Coll
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
reproductive system
• mutant ovaries exhibit primary and secondary follicles and occasionally an early antral follicle but no large graafian follicles (J:96442)
(J:96442)
• mutant uterine horns are thread-like (J:96442)
• mutant females show small vaginal openings (J:96442)
• no sperm are detected in the lumen of seminiferous tubules or the epididymis (J:96442)
• very few haploid spermatids are detected, although primary spermatocytes are present (J:96442)
• spermatogenesis is initiated but ceases prior to the meiotic-division stage (J:96442)
• both adult male and female mutants display hypogonadotropic hypogonadism
• mutant ovaries are significantly smaller than wild-type (J:96442)
• mean ovary weight is reduced to 17.5% of wild-type (J:96442)
• mutant testes are significantly smaller than wild-type (J:96442)
• mean testis weight is reduced to 28% of wild-type (J:96442)
• adult homozygotes are viable but demonstrate pubertal delay
• sexual infantilism can be corrected by the administration of exogenous gonadotropin-releasing hormone
• mutant females fail to ovulate (J:96442)
• however, ovulation can be induced after sequential injection of the gonadotropins pregnant mares serum and human chorionic gonadotropin (J:96442)
• vaginal smears consist of non-keratinized epithelia and mucus strands similar to those seen in immature females (J:96442)
• mutant females fail to become pregnant after appropriate mating exposure (J:96442)

endocrine/exocrine glands
• in mutant adrenal glands, the prepubescent zone X, which normally regresses at puberty, is still present in the innermost region of the cortex
• mutant female show reduced mammary-duct formation (J:96442)
• no postpubertal maturation of branched epithelial ducts is observed (J:96442)
• mutant ovaries exhibit primary and secondary follicles and occasionally an early antral follicle but no large graafian follicles (J:96442)
• mutant ovaries are significantly smaller than wild-type (J:96442)
• mean ovary weight is reduced to 17.5% of wild-type (J:96442)
• mutant testes are significantly smaller than wild-type (J:96442)
• mean testis weight is reduced to 28% of wild-type (J:96442)

homeostasis/metabolism
• mutant males show significantly lower blood testosterone concentrations than wild-type controls
• testosterone concentrations in male mutants mice are similar to those observed in wild-type females
• female mutants display 17beta-estradiol concentrations that are similar to those in wild-type females at nonestrus stages and to base-line serum estradiol concentrations in wild-type males
• adult mutant mice exhibit low circulating gonadotropin concentrations relative to wild-type controls
• however, mutant gonads remain sensitive to exogenous gonadotropins while pituitary gonadotropes remain responsive to stimulation by gonadotropin-releasing hormone
• moreover, mutant hypothalamic extracts show normal gonadotropin-releasing hormone concentrations despite observed hypogonadotropism
• in response to kisspeptins, homozygous mutants do not exhibit a rise in plasma follicle stimulating hormone levels as occurs in wild-type controls (J:96108)
• both adult male and female mutants show a significant reduction in serum follicle-stimulating hormone levels relative to wild-type controls (J:96442)
• in response to kisspeptins (a ligand for Gpr54), homozygous mutants do not exhibit a rise in plasma luteinizing hormone levels as occurs in wild-type controls (J:96108)
• both adult male and female mutants show a moderate reduction in serum luteinizing hormone levels relative to wild-type controls (J:96442)

behavior/neurological
• no sexual mounting behavior is observed among mutant males (J:96442)

nervous system
N
• gonadotropin-releasing hormone neurons appear normal and exhibit correct projection into the median eminence (J:96108)
• no gross morphologic abnormalities are detected in the central nervous system (J:96442)

renal/urinary system

integument
• mutant female show reduced mammary-duct formation (J:96442)
• no postpubertal maturation of branched epithelial ducts is observed (J:96442)

Mouse Models of Human Disease
OMIM IDRef(s)
Hypogonadotropic Hypogonadism 8 with or without Anosmia; HH8 614837 J:96442