Phenotypes for Lrp8 MGI:2182097 MGI Mouse

• male homozygotes display abnormal sperm maturation in the proximal epididymis

• however, mutant testicular and epididymal structures exhibit normal development, and spermatozoa descending from the seminiferous tubules of the testis into the initial segment of the epididymis are morphologically normal

abnormal sperm flagellum morphology ( J:84102 )

• after exit from the initial epididymal segment, distinct tail abnormalities are increasingly observed during transit of sperm through the epididymal duct

abnormal sperm midpiece morphology ( J:84102 )

• some sperm mid-pieces show abnormal kinking and fraying of axonemal structures

abnormal sperm mitochondrial sheath morphology ( J:84102 )

• unlike wild-type, most mutant spermatozoa exhibit a highly irregular mitochondrial helix in mid-piece sections of the sperm tail

coiled sperm flagellum ( J:84102 )

• ~51% of mutant spermatozoa from the cauda epididymidis display coiling of the tail with a variable degree of bending

• ~49% show normal straight tail morphology

hairpin sperm flagellum ( J:84102 )

• 43% of mutant spermatozoa from the cauda epididymidis exhibit hairpin structures (180 degrees)

• hairpin morphology is completely reverted upon incubation in buffer containing mild detergents (0.1% Triton X-100), indicating cell volume dysregulation

kinked sperm flagellum ( J:84102 )

• 8% of mutant spermatozoa from the cauda epididymidis show slight angulations (<90 degrees)

male infertility ( J:55691 , J:84102 )

(J:55691)

• male infertility is associated with reduced expression of a sperm maturation protein (GPX4) in the epididymis (J:84102)

abnormal sperm physiology ( J:84102 )

• mutant spermatozoa from the cauda epididymidis fail to regulate the intracellular osmotic pressure ("cell volume decrease")

• as a result, sperm fail to counteract water influx when released into hypo-osmotic conditions, causing cell swelling and coiling of the sperm tail

asthenozoospermia ( J:84102 )

• the % of motile mutant sperm is reduced to half the wild-type control value

• although curvilinear velocity and the amplitude of lateral head displacement remain normal, all other sperm analysis parameters are significantly reduced indicating ineffective forward progression

abnormal contextual conditioning behavior ( J:55691 )

• contextual fear-conditioned learning deficits

abnormal spatial learning ( J:100988 )

• homozygotes spent less time in the training quadrant and crossed the former platform position less often in probe trials compared to wild-type mice

abnormal neuronal migration ( J:117956 )

• corticospinal neurons are mislocalized to layers 4 and 6 of cerebral cortex

abnormal brain development ( J:55691 )

• cortical layering disrupted, with neurons packed into tight horizontal layers

reduced cerebellar foliation ( J:55691 )

• less foliated than wild-type

abnormal dentate gyrus morphology ( J:55691 , J:105699 )

• neurons in the dentate gyrus were very loosely packed (J:55691)

• ectopic calbindin-positive cells are located mainly in the polymorph layer between the densely packed granule layers (J:105699)

abnormal hippocampus layer morphology ( J:105699 )

• ectopic calbindin-positive cells are located mainly in the polymorph layer between the densely packed granule layers

abnormal cerebral cortex morphology ( J:105699 )

• at P21, markers for cortical layer 6 and subplate neurons have broadened expression, indicating that neurons are infiltrating layers closer to the cortical surface

abnormal Purkinje cell morphology ( J:55691 )

• abnormal aggregates of Purkinje cells and cortical neurons

small cerebellum ( J:55691 )