Phenotypes Associated with This Genotype

Genotype
MGI:3583221

• Allelic Composition: Fkbp4^tm1Dvds/Fkbp4^tm1Dvds
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

cellular

asthenozoospermia ( J:98554 )

♂ • reduced motility in vitro

mortality/aging

prenatal lethality, incomplete penetrance ( J:98554 )

• partial embryonic lethality, observed approximately 50% the expected Mendelian ratio

reproductive system

abnormal prostate gland morphology ( J:98554 )

♂ • dorsolateral and ventral prostate lobes were less affected than anterior prostate, but had mildly dysgenic features

absent prostate gland anterior lobe ( J:98554 )

♂ • reduced or absent anterior prostate

small prostate gland anterior lobe ( J:98554 )

♂ • reduced or absent anterior prostate

abnormal seminal vesicle morphology ( J:98554 )

♂ • were always malformed, however testicular histology appeared normal and all stages of spermatogenesis were observed

small seminal vesicle ( J:98554 )

♂ • often, seminal vesicles were around 50% of normal size on both sides, but could vary between left and right lobes and could range from about 80% of normal size to being absent

abnormal testis morphology ( J:98554 )

♂

unilateral cryptorchism ( J:98554 )

♂ • 5/20 had unilateral undescended testis

ambiguous external male genitalia ( J:98554 )

♂ • 15/20 males had ambiguous external genitalia

abnormal secondary sex determination ( J:98554 )

• displayed incomplete virilization

male pseudohermaphroditism ( J:98554 )

♂ • 15/20 males had ambiguous external genitalia and 14/20 males had easily observable nipples and areolas

abnormal reproductive system physiology ( J:98554 )

asthenozoospermia ( J:98554 )

♂ • reduced motility in vitro

abnormal luminal closure ( J:101405 )

♀ • on day 4 of pregnancy (when the uterus is under P4 influence), mutant uteri displayed reduced luminal closure and luminal epithelial proliferation while wild-type uteri exhibited luminal closure with intense stromal cell proliferation

failure of embryo implantation ( J:101405 )

• complete implantation failure due to lack of attainment of uterine receptivity

abnormal uterine receptivity ( J:101405 )

♀ • the uterus was completely nonreceptive to blastocyst implantation as a result of impaired progesterone (P₄) functions, including a 2-fold reduction in P₄ binding to the nuclear progesterone receptor (PR), a fractional reduction in the number of P₄ binding sites, attenuated PR transcriptional activity, and down-regulation of several P₄-regulated genes in the uterus

female infertility ( J:101405 )

♀ • female homozygotes mated with wild-type fertile males failed to produce any offspring due to a complete implantation failure

male infertility ( J:98554 , J:101405 )

♂ • multiple attempts to mate males with mild defects to wild-type females failed to result in pregnancy (J:98554)

♂ • male homozygotes are infertile due to partial androgen insensitivity with ambiguous external genitalia (J:101405)

impaired fertilization ( J:98554 , J:101405 )

• spermatozoa isolated from the epididymis exhibited reduced fertilization efficiency in vitro (J:98554)

• both in vivo and in vitro fertilization rates of ova arising from mutant females were reduced relative to wild-type females (J:101405)

• however, the number of normally ovulated or superovulated ova in mutant females was comparable to that of wild-type females, indicating normal ovulation (J:101405)

endocrine/exocrine glands

abnormal prostate gland morphology ( J:98554 )

♂ • dorsolateral and ventral prostate lobes were less affected than anterior prostate, but had mildly dysgenic features

absent prostate gland anterior lobe ( J:98554 )

♂ • reduced or absent anterior prostate

small prostate gland anterior lobe ( J:98554 )

♂ • reduced or absent anterior prostate

abnormal seminal vesicle morphology ( J:98554 )

♂ • were always malformed, however testicular histology appeared normal and all stages of spermatogenesis were observed

small seminal vesicle ( J:98554 )

♂ • often, seminal vesicles were around 50% of normal size on both sides, but could vary between left and right lobes and could range from about 80% of normal size to being absent

abnormal testis morphology ( J:98554 )

♂

unilateral cryptorchism ( J:98554 )

♂ • 5/20 had unilateral undescended testis

renal/urinary system

hypospadia ( J:98554 )

• all males had mild to severe hypospadia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
androgen insensitivity syndrome		DOID:4674	OMIM:300068	J:98554