Phenotypes associated with this allele

• Allele Symbol: Fkbp4^tm1Dvds
• Allele Name: targeted mutation 1, David F Smith
• Allele ID: MGI:3579432
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fkbp4^tm1Dvds/Fkbp4^tm1Dvds	either: (involves: CD-1) or (involves: 129X1/SvJ * C57BL/6)	MGI:3818988
hm2	Fkbp4^tm1Dvds/Fkbp4^tm1Dvds	involves: 129X1/SvJ * C57BL/6	MGI:3583221

Genotype
MGI:3818988

hm1

• Allelic Composition: Fkbp4^tm1Dvds/Fkbp4^tm1Dvds
• Genetic Background: either: (involves: CD-1) or (involves: 129X1/SvJ * C57BL/6)

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

reproductive system

hairpin sperm flagellum ( J:118360 )

♂ • ~40% of mutant sperm isolated from the cauda epididymis display abnormal flagellar morphology (hairpin bends)

♂ • in contrast, mutant sperm isolated from the caput and corpus regions of the epididymis show normal morphology

oligozoospermia ( J:118360 )

♂ • male homozygotes show a significant reduction of epididymal sperm count relative to wild-type males

male infertility ( J:118360 )

♂ • matings between male homozygotes with minimal penile dysgenesis and wild-type females fail to produce vaginal plugs

impaired fertilization ( J:118360 )

• Background Sensitivity: reduction of in vitro fertilizing capacity of mutant sperm is less severe on a CD-1 genetic background than on a mixed 129 x C57BL/6 background

• in vitro fertilizing capacity of mutant sperm isolated from 129 x C57BL/6 males is significantly lower than that of background-matched wild-type sperm (44% vs 76%, respectively); however, a comparable % of fertilized embryos develop to the blastocyst stage (88% vs 91%, respectively)

• in vitro fertilizing capacity of mutant sperm isolated from CD-1 males is also lower than that of CD-1 wild-type sperm (73% vs 93%, respectively); again, a comparable % of fertilized embryos develop to the blastocyst stage (88% vs 90%, respectively)

• no significant differences in the induction of acrosome reaction are observed between wild-type and mutant sperm in response to the calcium ionophore A23187

cellular

hairpin sperm flagellum ( J:118360 )

♂ • ~40% of mutant sperm isolated from the cauda epididymis display abnormal flagellar morphology (hairpin bends)

♂ • in contrast, mutant sperm isolated from the caput and corpus regions of the epididymis show normal morphology

oligozoospermia ( J:118360 )

♂ • male homozygotes show a significant reduction of epididymal sperm count relative to wild-type males

Genotype
MGI:3583221

hm2

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

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