All Phenotypes Far1<em1(IMPC)Wtsi> MGI Mouse

decreased survivor rate ( J:339470 )

• mice are subviable with a marked variability in lifespans; however, mice that pass a critical stage before weaning are able to survive like wild-type and heterozygous littermates

preweaning lethality, incomplete penetrance ( J:339470 )

• over 70% of mice die embryonically or perinatally, with only 7% of homozygotes recovered at weaning

decreased body weight ( J:339470 )

• surviving mice weigh significantly less than control littermates from 4 to 12 weeks of age

postnatal growth retardation ( J:339470 )

• surviving mice display growth retardation

• however, at birth, pups appear indistinguishable from control littermates

decreased male germ cell number ( J:339470 )

• mice exhibit significantly fewer germ cells in the seminiferous tubules

multinucleated giant male germ cells ( J:339470 )

• very large multinucleated giant cells (MGCs), some larger than 50 um in diameter, are found lining the lumen of seminiferous tubules and consist of numerous round spermatids

• punctate DAZL signals are detected in the MGCs in the seminiferous tubule lumen

• patchy Tex14 staining is observed on the MGC membrane, suggesting disrupted ICBs as a cause of MGC formation

• however, large MGCs are absent in the epididymal lumen

increased male germ cell apoptosis ( J:339470 )

• TUNEL staining showed massive germ cell apoptosis; many of the large multinucleated giant cells (MGCs) lining the lumen of seminiferous tubules undergo apoptosis

• both the number of TUNEL+ apoptotic cells per seminiferous tubule and the % of TUNEL+ tubules are significantly increased

abnormal seminiferous tubule morphology ( J:339470 )

• seminiferous tubules contain significantly fewer cells, with no elongated spermatids or spermatozoa found in the seminiferous epithelium

small testis ( J:339470 )

• testes appear smaller at 4 months of age

decreased testis weight ( J:339470 )

• at 4 months of age, testis weight is significantly less than that in control males

abnormal spermatogenesis ( J:339470 )

• round spermatids are present, but no elongated spermatids or mature spermatozoa are detected

• immunostaining of TEX14, an intercellular bridge (ICB) marker, showed very few punctate TEX14 signals in the seminiferous tubules, indicating defective ICB formation/stabilization; TEX14 puncta per nucleus is reduced by >50%

• TEX14 is found on the MGC membrane in an aberrant patchy pattern, indicating impaired ICB protein complex assembly and targeting

azoospermia ( J:339470 )

• males produce no sperm; cauda epididymis lumen contains cellular debris and round bodies (likely degenerative residual bodies or sloughed germ cells) but no normal spermatozoa

abnormal spermatocyte morphology ( J:339470 )

• some of the DAZL-positive (also SCP3-positive) spermatocytes become disorganized and are found near the seminiferous tubule lumen

arrest of spermatogenesis ( J:339470 )

• PNA staining appears as small punctate dots in the testicular germ cell layers and as large bright clusters within the MGCs at the lumen, indicating a spermatogenesis arrest at the round spermatid stage

male infertility ( J:339470 )

• adult male mice are infertile