All Phenotypes Acrbp<tm1Tba> MGI Mouse

reproductive system phenotype ( J:234286 )

N	• females exhibit normal fertility relative to controls • males show normal testicular weight and number of cauda epididymal sperm relative to controls

abnormal sperm midpiece morphology ( J:234286 )

• in type 4 sperm, the midpiece is coiled around the deformed nucleus

• however, the flagella show a normal 9 + 2 microtubule axoneme

abnormal acrosome morphology ( J:234286 )

• cauda epididymal sperm show a continuous variation in the shapes of the acrosome and nucleus, divided into morphological types 1, 2, 3, and 4 (~50%, 34%, 12%, and 4% of total sperm, respectively)

• in type 1 sperm, nuclear shape is normal, but the acrosome is partially fragmented on the head or is not fully elongated at the dorsal edge

• in type 2 and type 3 sperm, nuclear shape is moderately and severely affected, respectively, and the acrosome structure is also fragmented

• in type 4 sperm, the acrosome is fragmented and a round-headed shape with a coiled midpiece around the deformed nucleus is observed

• TEM analysis revealed that all types of epididymal sperm exhibit a deformed acrosome; however, type 4 sperm are rarely found in the testis

• fragmented acrosomal structure of elongating spermatids and epididymal sperm is restored to a nearly normal level by exogenous ACRBP-V5 expression

abnormal acrosome assembly ( J:234286 )

• although proacrosomal vesicles assemble normally in the Golgi phase, early spermatids fail to form a large acrosomal granule in the center of acrosomal vesicle and show a diffuse pattern of head cap distribution in the anterior region of the nucleus in the cap-phase; acrosomal structure is severely deformed at later steps of spermiogenesis

• TEM imaging confirmed the presence of an abnormally shaped acrosomal vesicle and lack of the electron-dense acrosomal granule in the center of acrosomal vesicle in the cap-phase; these defects become more severe as spermiogenesis proceeds

globozoospermia ( J:234286 )

• ~4% of epididymal sperm (type 4) are round-headed but still possess a fragmented acrosome on the head, suggesting that ACRBP may not be directly involved in a globozoospermia-related phenotype

abnormal sperm nucleus morphology ( J:234286 )

• in type 2 and type 3 sperm, nuclear shape is moderately and severely affected, respectively

• in type 4 sperm, a coiled midpiece is found around the deformed nucleus

• in type 2, type 3 and type 4 sperm, the nucleus is abnormally condensed

• in type 1 sperm, nuclear shape is normal

impaired sperm migration in female genital tract ( J:294381 )

• 2 h after mating with wild-type females, the number of sperm recovered from the oviduct is significantly smaller than that for wild-type sperm, whereas the number of sperm recovered from the uterus is normal at 1.5 h after mating

• 4 h after mating, >80% of total sperm in the oviduct correspond to type 1 sperm whereas proportions of type 2 and type 3 sperm are ~15% and 3%, respectively, and no type 4 sperm is found in the oviduct

abnormal sperm motility ( J:234286 , J:294381 )

• type 1 and type 2 sperm exhibit irregular patterns of flagellar beating and head rotations (J:234286)

• type-3 sperm show dysfunctional flagellar beating (J:234286)

• at 1.5 h after mating, type 1 and type 2 uterine sperm exhibit slightly anomalous patterns of movement trajectories, whereas type 3 and type 4 uterine sperm show dysfunctional flagellar beating and loss of forward movement, respectively (J:294381)

• however, type 1 and type 2 oviductal sperm show normal movement trajectories at 4 h after mating (J:294381)

decreased sperm progressive motility ( J:234286 , J:294381 )

• progressive motility is significantly reduced (J:234286)

• at 1.5 h after mating, type 4 uterine sperm show loss of forward movement (J:294381)

asthenozoospermia ( J:234286 , J:294381 )

• total motility, rapid motility, and hyperactivated motility of capacitated epididymal sperm are significantly reduced (J:234286)

• type-4 sperm show loss of or no forward movement (J:234286)

• type 1/type 2 and type 3 sperm show a modest and severe reduction, respectively, in the bending motion of the midpiece (J:234286)

• at 1.5 h after mating, type 1 and type 2 uterine sperm show significantly lower velocity ratios, linearity (LIN) and wobble (WOB) than wild-type sperm (J:294381)

• all kinetic parameters of type 3 and type 4 uterine sperm, except for STR (straightness), are decreased (J:294381)

• however, type 1 and type 2 uterine sperm show normal VCL (curvilinear velocity), VAP (average path velocity) and VSL (straight-line velocity) (J:294381)

• all kinetic parameters of sperm recovered from the oviduct are normal, suggesting that sperm already migrated into the ovary retain normal motility (J:294381)

decreased hyperactivated sperm motility ( J:234286 )

• hyperactivated motility is significantly reduced

immotile sperm ( J:234286 )

• capacitated epididymal sperm display a remarkably high rate of static cells

abnormal spermiogenesis ( J:234286 )

decreased litter size ( J:234286 )

• when mated with wild-type females, male mice sire significantly smaller litter sizes than control males

male infertility ( J:234286 )

• 3 of 10 males produced no offspring one month after mating with wild-type females

• however, plug formation is normal

reduced male fertility ( J:234286 )

• male fertility is severely reduced

• however, fertility is significantly restored by introduction either of exogenous ACRBP-W or ACRBP-V

abnormal sperm-egg fusion ( J:234286 )

• in vitro, the ability of capacitated sperm to fuse with the ZP-free oocytes is markedly reduced

decreased fertilization frequency ( J:234286 )

• when cumulus-intact oocytes are used, in vitro fertilization (IVF) rate is less than 10% of that in wild-type sperm

• however, after intracytoplasmic sperm injection (ICSI), most oocytes microinjected with the heads of type 1/type 2 or type 3 sperm (or the whole cell for type 4 sperm) are successfully activated and reach the 2-cell stage

impaired binding of sperm to zona pellucida ( J:234286 )

• in vitro, the ability of capacitated sperm to bind the cumulus-free oocyte zona pellucida (ZP) is markedly reduced