Phenotypes associated with this allele

• Allele Symbol: Lhcgr^tm1Hht
• Allele Name: targeted mutation 1, Ilpo Huhtaniemi
• Allele ID: MGI:2181999
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lhcgr^tm1Hht/Lhcgr^tm1Hht	involves: 129S7/SvEvBrd * C57BL/6J	MGI:2182003

Genotype
MGI:2182003

hm1

• Allelic Composition: Lhcgr^tm1Hht/Lhcgr^tm1Hht
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

oligozoospermia ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, the number of spermatozoa in cauda epididymis is lower and highly variable in treated male homozygotes relative to wild-type males (3.2 3.2 vs. 12.4 3.2 x 10⁶), indicating that quantitative spermatogenesis is incompletely restored

♂ • in contrast, the motility and shape of spermatozoa appear normal following high-dose testosterone treatment

reproductive system

oligozoospermia ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, the number of spermatozoa in cauda epididymis is lower and highly variable in treated male homozygotes relative to wild-type males (3.2 3.2 vs. 12.4 3.2 x 10⁶), indicating that quantitative spermatogenesis is incompletely restored

♂ • in contrast, the motility and shape of spermatozoa appear normal following high-dose testosterone treatment

abnormal anogenital distance ( J:66818 , J:105533 )

• described as short at >30-35 days after birth (J:66818)

• during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, the anogenital distance reaches wild-type values (J:105533)

abnormal female reproductive system morphology ( J:66818 )

♀

absent corpus luteum ( J:66818 )

♀ • at 7 weeks of age

absent mature ovarian follicles ( J:66818 )

♀ • no pre-ovulatory follicles are observed at the age of 7 and 12 weeks

impaired ovarian folliculogenesis ( J:66818 )

♀ • follicles appear up to early antral stage, but no pre-ovulatory follicles or corpora lutea are observed at the age of 7 and 12 weeks

small ovary ( J:66818 )

♀ • mutant ovaries are about 50% smaller than wild-type

abnormal uterus morphology ( J:66818 )

♀

absent endometrial glands ( J:66818 )

♀ • absence of uterine glandular structures

thin uterine horn ( J:66818 )

♀

thin uterus ( J:66818 )

♀ • thinning of uterine cell layers

arrest of spermatogenesis ( J:66818 , J:105533 )

♂ • spermatogenesis is arrested at stage 6 round spermatids (J:66818)

♂ • after high-dose testosterone replacement therapy initiated at P21, spermatogenesis is restored in the testes, although absence of Leydig cells between tubules is still evident (J:105533)

abnormal male reproductive system morphology ( J:66818 )

♂

bulbourethral gland hypoplasia ( J:105533 )

♂ • macroscopically undetectable at 11 weeks of age

♂ • high-dose testosterone replacement initiated at the prepubertal age (P21) causes the severely hypoplastic bulbourethral glands to become detectable

abnormal prostate gland morphology ( J:105533 )

♂ • the prostate shows histological resemblance to the undifferentiated state found in newborn pups

♂ • after high-dose testosterone replacement therapy initiated at P21, prostates grow considerably and attain wild-type histology

small prostate gland anterior lobe ( J:105533 )

♂ • coagulating glands are small

♂ • after high-dose testosterone replacement therapy initiated at P21, coagulating glands grow considerably and attain wild-type histology

prostate gland hypoplasia ( J:66818 )

♂ • too small to detect or absent at 7 weeks of age

♂ • during high-dose testosterone replacement initiated at the prepubertal age (P21), the severely hypoplastic prostate gland grows significantly to reach wild-type size and weight

small seminal vesicle ( J:105533 )

♂

seminal vesicle hypoplasia ( J:66818 )

♂ • too small to detect or absent at 7 weeks of age

♂ • during high-dose testosterone replacement initiated at the prepubertal age (P21), the severely hypoplastic seminal vesicles grow significantly and their weights exceed those of wild-type mice

♂ • in addition, testosterone-treated seminal vesicles attain wild-type histology

small seminiferous tubules ( J:66818 , J:105533 )

♂ • narrow seminiferous tubules at 7 weeks of age (J:66818)

♂ • during high-dose testosterone replacement therapy initiated at the prepubertal age (P21), the diameter of seminiferous tubules is increased to nearly the size of wild-type tubules (J:105533)

decreased Leydig cell number ( J:66818 , J:105533 )

♂ • the numbers and sizes of Leydig cells are severely reduced at 45 days after birth (J:66818)

♂ • the number and size of Leydig cells is severely reduced in the interstitial space, as shown by a 89% reduction in interstitial cell mass per testis (J:105533)

♂ • after high-dose testosterone replacement therapy, the mass of interstitial cells remains persistently low, eventhough the width of seminiferous tubules is increased and spermatogenesis is restored in the testes (J:105533)

absent Leydig cells ( J:66818 )

♂ • adult-type Leydig cells are absent

small testis ( J:66818 )

♂ • very small at 7 weeks of age

decreased testis weight ( J:66818 , J:105533 )

♂ • 20% of wild-type weight at 7 weeks of age (J:66818)

♂ • after high-dose testosterone replacement therapy initiated at P21, mutant testis weights are indistinguishable from those of wild-type males (J:105533)

cryptorchism ( J:66818 , J:105533 )

♂ • testes are located in the abdominal cavity adjacent to the urinary bladder at 7 weeks of age (J:66818)

♂ • high-dose testosterone replacement therapy initiated at the prepubertal age (P21) causes cryptorchid testes to descend into the scrotum (J:105533)

small penis ( J:66818 , J:105533 )

♂ • at >30-35 days after birth (J:66818)

♂ • during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, the underdeveloped penis attains the size of wild-type (J:105533)

scrotum hypoplasia ( J:66818 , J:105533 )

♂ • underdeveloped at >30-35 days after birth (J:66818)

♂ • during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, the underdeveloped scrotum attains the size of wild-type (J:105533)

external male genitalia atrophy ( J:105533 )

♂ • accessory sex organs are atrophic

♂ • after high-dose testosterone replacement therapy initiated at the prepubertal age (P21), male homozygotes are externally indistinguishable from wild-type males

abnormal caput epididymis morphology ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, epithelial cells in the caput region remain partially disorganized and contain multiple vacuoles, while all principal cells fail to display a normal arrangement around the lumen

♂ • however, the expression of several epididymis-specific genes in caput epididymis is restored, and the corpus and cauda of testosterone-treated male homozygotes appear histologically normal

epididymis hypoplasia ( J:66818 )

♂ • too small to detect or absent at 7 weeks of age

♂ • during high-dose testosterone replacement initiated at the prepubertal age (P21), the severely hypoplastic epididymis grows significantly to reach wild-type size and weight

vas deferens hypoplasia ( J:105533 )

♂ • the vasa deferentia are severely hypoplastic

♂ • after high-dose testosterone replacement therapy initiated at P21, vasa deferentia attain wild-type histology, and the glandular lumina and vasa deferentia appear open; however, some male homozygotes develop inflammation associated with abnormal epithelial structure of vasa deferentia

delayed vaginal opening ( J:66818 )

• vaginal opening is delayed to 35-38 days versus 30-32 days in wild-type mice

abnormal reproductive system physiology ( J:66818 )

prostate gland inflammation ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, 4 of 6 male homozygotes develop vigorous inflammation of the prostate gland

♂ • some acini show abnormal epithelial architecture and are filled with necrotic mass while others show normal histology

♂ • lymphocyte accumulation is observed in stromal tissue and between tissue layers in prostates and vasa deferentia, and the inflammation is associated with abnormal epithelial structure of vasa deferentia

decreased ovary secretion ( J:66818 )

♀ • significantly decreased ovarian estradiol and progesterone levels at 7 weeks of age

decreased testes secretion ( J:66818 )

♂ • significantly decreased testicular testosterone levels at 7 weeks of age

reproductive system inflammation ( J:105533 )

• after high-dose testosterone treatment initiated at P21, 4 of 6 male homozygotes exhibit inflammation of the prostate, coagulating glands, and vasa deferentia, as shown by the accumulation of lymphocyte and neutrophilic cells

epididymis inflammation ( J:105533 )

• after high-dose testosterone replacement therapy initiated at P21, some male homozygotes develop severe inflammation in the epididymis, as shown by the accumulation of necrotic cell masses

absent estrus ( J:66818 )

♀ • no recognizable estrous at 12 weeks of age

absent estrous cycle ( J:66818 )

♀ • no estrous cyclicity at 12 weeks of age

female infertility ( J:66818 )

♀

male infertility ( J:66818 )

♂

reduced male fertility ( J:105533 )

♂ • after high-dose testosterone replacement therapy, male homozygotes remain subfertile, as only 9% of all breedings result in pregnancy, and only two of 13 mice (15%) are proven fertile

♂ • however, the average litter size and number of fertilized oocytes detected in the oviducts of females mated with testosterone-treated male homozygotes vary within normal range, and offspring are healthy and grow normally

abnormal ejaculation ( J:105533 )

♂ • only 46% (6 of 13) of testosterone-treated male homozygotes are able to ejaculate (at least occasionally), as determined by vaginal plugs

♂ • the ejaculating frequency is severely reduced

♂ • as a result, only 23% (18 of 78) of females, bred with testosterone-treated male homozygotes, exhibit vaginal plugs

♂ • few spermatozoa are found in vaginal plugs, indicating reduced transfer of spermatozoa from the epididymis to the ejaculate

abnormal sperm physiology ( J:105533 )

♂ • after high-dose testosterone replacement therapy, spermatozoa are able to fertilize oocytes, but their passage from epididymis to uterus is impaired

homeostasis/metabolism

decreased circulating testosterone level ( J:66818 , J:105533 )

• significantly decreased serum testosterone levels at 7 weeks of age (J:66818)

• untreated male homozygotes display severely reduced, although still detectable, serum testosterone levels at 11 weeks of age (J:105533)

• high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days causes an 8-fold increase in mean serum testosterone levels relative to wild-type values (J:105533)

increased circulating follicle stimulating hormone level ( J:66818 , J:105533 )

• elevated serum FSH levels at 7 weeks of age; both males and females affected (J:66818)

• in contrast, pituitary FSH levels are reduced in both males and females (J:66818)

• male homozygotes display a ~3-fold increase in serum FSH levels relative to wild-type males (J:105533)

• high-dose testosterone treatment of male homozygotes initiated at P21 suppresses serum FSH levels to ~50% of wild-type male values (J:105533)

increased circulating luteinizing hormone level ( J:66818 , J:105533 )

• increased serum lutenizing hormone levels at 7 weeks of age; both males and females affected (J:66818)

• however, no significant differences in pituitary LH levels between wild-type, hetero- and homozygous mutants are observed (J:66818)

• male homozygotes show remarkably higher serum LH levels relative to wild-type males (J:105533)

• high-dose testosterone treatment of male homozygotes initiated at P21 reduces LH levels to nearly undetectable levels, indicating a normal feedback response to testosterone at the hypothalamic-pituitary level (J:105533)

immune system

prostate gland inflammation ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, 4 of 6 male homozygotes develop vigorous inflammation of the prostate gland

♂ • some acini show abnormal epithelial architecture and are filled with necrotic mass while others show normal histology

♂ • lymphocyte accumulation is observed in stromal tissue and between tissue layers in prostates and vasa deferentia, and the inflammation is associated with abnormal epithelial structure of vasa deferentia

enlarged spleen ( J:105533 )

• spleen size is increased at 11 weeks of age

• high-dose testosterone replacement therapy initiated at P21 restores spleen size to wild-type values

reproductive system inflammation ( J:105533 )

• after high-dose testosterone treatment initiated at P21, 4 of 6 male homozygotes exhibit inflammation of the prostate, coagulating glands, and vasa deferentia, as shown by the accumulation of lymphocyte and neutrophilic cells

epididymis inflammation ( J:105533 )

• after high-dose testosterone replacement therapy initiated at P21, some male homozygotes develop severe inflammation in the epididymis, as shown by the accumulation of necrotic cell masses

growth/size/body

decreased body weight ( J:66818 )

• mutant males are 30% lighter than wild-type male littermates after 45 days of age; mutant females are unaffected up to 7 weeks of age

increased kidney weight ( J:105533 )

• during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, mutant kidney weights show a notable response to elevated testosterone and increase above wild-type weights (treated vs untreated mutants vs wild-type, 9.7 0.80 vs. 4.2 0.47 vs. 5.7 0.65 mg/g BW)

• in contrast, liver and pituitary weights remain unchanged during testosterone treatment

enlarged spleen ( J:105533 )

• spleen size is increased at 11 weeks of age

• high-dose testosterone replacement therapy initiated at P21 restores spleen size to wild-type values

hematopoietic system

enlarged spleen ( J:105533 )

• spleen size is increased at 11 weeks of age

• high-dose testosterone replacement therapy initiated at P21 restores spleen size to wild-type values

renal/urinary system

increased kidney weight ( J:105533 )

• during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, mutant kidney weights show a notable response to elevated testosterone and increase above wild-type weights (treated vs untreated mutants vs wild-type, 9.7 0.80 vs. 4.2 0.47 vs. 5.7 0.65 mg/g BW)

• in contrast, liver and pituitary weights remain unchanged during testosterone treatment

small penis ( J:66818 , J:105533 )

♂ • at >30-35 days after birth (J:66818)

♂ • during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, the underdeveloped penis attains the size of wild-type (J:105533)

endocrine/exocrine glands

increased adrenal gland weight ( J:105533 )

• adrenal gland weights are increased at 11 weeks of age

enlarged adrenal glands ( J:105533 )

• after high-dose testosterone replacement therapy initiated at P21, mutant adrenal sizes are reduced but remain significantly larger than wild-type

bulbourethral gland hypoplasia ( J:105533 )

♂ • macroscopically undetectable at 11 weeks of age

♂ • high-dose testosterone replacement initiated at the prepubertal age (P21) causes the severely hypoplastic bulbourethral glands to become detectable

abnormal prostate gland morphology ( J:105533 )

♂ • the prostate shows histological resemblance to the undifferentiated state found in newborn pups

♂ • after high-dose testosterone replacement therapy initiated at P21, prostates grow considerably and attain wild-type histology

small prostate gland anterior lobe ( J:105533 )

♂ • coagulating glands are small

♂ • after high-dose testosterone replacement therapy initiated at P21, coagulating glands grow considerably and attain wild-type histology

prostate gland hypoplasia ( J:66818 )

♂ • too small to detect or absent at 7 weeks of age

♂ • during high-dose testosterone replacement initiated at the prepubertal age (P21), the severely hypoplastic prostate gland grows significantly to reach wild-type size and weight

small seminal vesicle ( J:105533 )

♂

seminal vesicle hypoplasia ( J:66818 )

♂ • too small to detect or absent at 7 weeks of age

♂ • during high-dose testosterone replacement initiated at the prepubertal age (P21), the severely hypoplastic seminal vesicles grow significantly and their weights exceed those of wild-type mice

♂ • in addition, testosterone-treated seminal vesicles attain wild-type histology

absent endometrial glands ( J:66818 )

♀ • absence of uterine glandular structures

absent corpus luteum ( J:66818 )

♀ • at 7 weeks of age

absent mature ovarian follicles ( J:66818 )

♀ • no pre-ovulatory follicles are observed at the age of 7 and 12 weeks

impaired ovarian folliculogenesis ( J:66818 )

♀ • follicles appear up to early antral stage, but no pre-ovulatory follicles or corpora lutea are observed at the age of 7 and 12 weeks

small ovary ( J:66818 )

♀ • mutant ovaries are about 50% smaller than wild-type

small seminiferous tubules ( J:66818 , J:105533 )

♂ • narrow seminiferous tubules at 7 weeks of age (J:66818)

♂ • during high-dose testosterone replacement therapy initiated at the prepubertal age (P21), the diameter of seminiferous tubules is increased to nearly the size of wild-type tubules (J:105533)

decreased Leydig cell number ( J:66818 , J:105533 )

♂ • the numbers and sizes of Leydig cells are severely reduced at 45 days after birth (J:66818)

♂ • the number and size of Leydig cells is severely reduced in the interstitial space, as shown by a 89% reduction in interstitial cell mass per testis (J:105533)

♂ • after high-dose testosterone replacement therapy, the mass of interstitial cells remains persistently low, eventhough the width of seminiferous tubules is increased and spermatogenesis is restored in the testes (J:105533)

absent Leydig cells ( J:66818 )

♂ • adult-type Leydig cells are absent

small testis ( J:66818 )

♂ • very small at 7 weeks of age

decreased testis weight ( J:66818 , J:105533 )

♂ • 20% of wild-type weight at 7 weeks of age (J:66818)

♂ • after high-dose testosterone replacement therapy initiated at P21, mutant testis weights are indistinguishable from those of wild-type males (J:105533)

cryptorchism ( J:66818 , J:105533 )

♂ • testes are located in the abdominal cavity adjacent to the urinary bladder at 7 weeks of age (J:66818)

♂ • high-dose testosterone replacement therapy initiated at the prepubertal age (P21) causes cryptorchid testes to descend into the scrotum (J:105533)

prostate gland inflammation ( J:105533 )

♂ • after high-dose testosterone replacement therapy initiated at P21, 4 of 6 male homozygotes develop vigorous inflammation of the prostate gland

♂ • some acini show abnormal epithelial architecture and are filled with necrotic mass while others show normal histology

♂ • lymphocyte accumulation is observed in stromal tissue and between tissue layers in prostates and vasa deferentia, and the inflammation is associated with abnormal epithelial structure of vasa deferentia

decreased ovary secretion ( J:66818 )

♀ • significantly decreased ovarian estradiol and progesterone levels at 7 weeks of age

decreased testes secretion ( J:66818 )

♂ • significantly decreased testicular testosterone levels at 7 weeks of age

digestive/alimentary system

abnormal anogenital distance ( J:66818 , J:105533 )

• described as short at >30-35 days after birth (J:66818)

• during high-dose testosterone replacement therapy initiated at the prepubertal age (P21) for 60 or 120 days, the anogenital distance reaches wild-type values (J:105533)

behavior/neurological

abnormal sexual interaction ( J:105533 )

♂ • after high-dose testosterone replacement therapy, male homozygotes exhibit normal mating behavior, although at lower frequency than wild-type controls