All Phenotypes Ccn6<tm1(cre)Mawa> MGI Mouse

Mouse Models of Human Disease	DO ID	OMIM ID(s)	Ref(s)
progressive pseudorheumatoid arthropathy of childhood	DOID:0090004	OMIM:208230	J:201718

oligozoospermia ( J:321647 )

• males show a ~5-fold reduction in cauda epididymal sperm number relative to control males

teratozoospermia ( J:321647 )

• males show a ~3-fold increase in morphologically abnormal cauda epididymidal sperm relative to control males

abnormal sperm midpiece morphology ( J:321647 )

• 63% of sperm show midpiece curling

kinked sperm flagellum ( J:321647 )

• 29% of sperm have bent tails, with flagella bent or folded at the annulus

multiflagellated sperm ( J:321647 )

• 2% of sperm have multiple tails

abnormal sperm head morphology ( J:321647 )

• 6% of sperm show head malformations

increased male germ cell apoptosis ( J:321647 )

• males show a 3-fold increase in spermatocyte apoptosis, as determined by co-staining with cleaved cPARP1 (a marker for apoptosis) and SYCP3 (a spermatocyte marker)

small testis ( J:321647 )

• adult testes are ~30% smaller than control testes

• however, testis histology shows complete spermatogenesis with supporting cells and multiple generations of germ cells

decreased testis weight ( J:321647 )

• adult testis weight is significantly lower than in control males

• however, adult body weight is normal

decreased litter size ( J:321647 )

• when adult males are bred with wild-type females for 4 months, average litter size is significantly lower than in control males

• however, total number of litters is normal

reduced male fertility ( J:321647 )

abnormal sperm physiology ( J:321647 )

• sperm lysates exhibit significantly reduced PPP1CC (protein phosphatase 1 catalytic subunit gamma, aka PP1) activity relative to lysates from control sperm

abnormal sperm motility ( J:321647 )

• specific sperm motility parameters, including % progressive motility, path velocity (VAP), curvilinear velocity (VCL) and relative motility index (RMI = % motility x straight line velocity (VSL)/100), are all significantly increased relative to controls

• however, % total motility and other parameters including lateral amplitude (ALH), beat frequency (BCF), straightness (STR), and linearity (LIN) are not significantly altered

increased sperm progressive motility ( J:321647 )

• sperm progressive motility is increased by 25% relative to that in control males