Phenotypes associated with this allele

• Allele Symbol: Ppp1cc^tm1Var
• Allele Name: targeted mutation 1, Susannah Varmuza
• Allele ID: MGI:2182577
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ppp1cc^tm1Var/Ppp1cc^tm1Var	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:2663275
hm2	Ppp1cc^tm1Var/Ppp1cc^tm1Var	involves: CD-1	MGI:4366538

Genotype
MGI:2663275

hm1

• Allelic Composition: Ppp1cc^tm1Var/Ppp1cc^tm1Var
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

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

reproductive system

decreased male germ cell number ( J:52211 )

♂ • decrease in the number of spermatids, particularly steps 8-16 elongating and condensing spermatids

oligozoospermia ( J:52211 )

♂ • occasional motile sperm, however round spermatids were the predominant germ cell in the cauda epididymis

abnormal male meiosis ( J:52211 )

♂ • spermatid abnormalities, such as polyploidy, indicating meiotic defects

small seminiferous tubules ( J:52211 )

♂ • decreased diameter

small testis ( J:52211 )

♂

abnormal spermiogenesis ( J:52211 )

♂ • defective spermiogenesis, leading to an apparent failure of spermiation

male infertility ( J:52211 )

♂

endocrine/exocrine glands

small seminiferous tubules ( J:52211 )

♂ • decreased diameter

small testis ( J:52211 )

♂

cellular

decreased male germ cell number ( J:52211 )

♂ • decrease in the number of spermatids, particularly steps 8-16 elongating and condensing spermatids

oligozoospermia ( J:52211 )

♂ • occasional motile sperm, however round spermatids were the predominant germ cell in the cauda epididymis

abnormal male meiosis ( J:52211 )

♂ • spermatid abnormalities, such as polyploidy, indicating meiotic defects

Genotype
MGI:4366538

hm2

• Allelic Composition: Ppp1cc^tm1Var/Ppp1cc^tm1Var
• Genetic Background: involves: CD-1

reproductive system

abnormal sperm flagellum morphology ( J:122018 )

♂ • testicular sperm exhibit a variety of tail defects, suggesting a role for the PP1gamma2 isoform (whose expression increases significantly during spermiogenesis in wild-type testes) in sperm tail morphogenesis

abnormal outer dense fiber morphology ( J:122018 )

♂ • in the principal sperm piece, outer dense fibers (ODFs) appear disorganized

♂ • many extra ODF florets (total of 13) are observed throughout the sperm flagella

abnormal sperm midpiece morphology ( J:122018 )

♂ • testicular sperm midpieces exhibit disorganized mitochondrial sheaths or appear thinner than the principal pieces due to absence of mitochondrial sheaths

abnormal sperm mitochondrial sheath morphology ( J:122018 )

♂ • mitochondrial sheaths of elongating spermatids and testicular spermatozoa appear disorganized and do not form the tightly packed helical structures found in wild-type sperm

absent sperm mitochondrial sheath ( J:122018 )

♂ • in some cases, mitochondrial sheaths are absent in testicular sperm

abnormal sperm principal piece morphology ( J:122018 )

♂ • in the principal sperm piece, outer dense fibers (ODFs) appear disorganized

♂ • many extra ODF florets (total of 13) are observed throughout the sperm flagella

abnormal sperm fibrous sheath morphology ( J:122018 )

♂ • a mild developmental abnormality of the fibrous sheath (FS) is observed, specifically in the morphology of its longitudinal columns, consistent with reduced or absent FS-specific protein expression

multiflagellated sperm ( J:82546 )

♂ • testicular sperm often display multiple tails

oligozoospermia ( J:82546 , J:122018 )

♂ • male homozygotes are severely oligospermic; most homozygotes do not shed any sperm into the epididymis (J:82546)

♂ • epididymides are virtually devoid of sperm; only immature germ cells, including round spermatids and, occasionally, pachytene spermatocytes, are observed (J:122018)

♂ • testicular sperm are present, although at reduced numbers relative to those found in wild-type testes (J:122018)

abnormal sperm head morphology ( J:82546 , J:122018 )

♂ • testicular sperm typically exhibit misshapen heads (J:82546)

♂ • all testicular sperm exhibit a range of aberrant head shapes, from round to oblong (J:122018)

globozoospermia ( J:122018 )

♂

pinhead sperm ( J:122018 )

♂

abnormal spermatid morphology ( J:122018 )

♂ • the number of mature elongated spermatids is severely reduced near the lumen of seminiferous tubules

♂ • degeneration of condensing spermatids, characterized by fragmentation of tail structures and the presence of numerous vacuoles in the cytoplasm of elongated spermatids, is observed

♂ • in contrast, the number of round spermatids is relatively normal in some seminiferous tubules

abnormal seminiferous tubule morphology ( J:122018 )

♂ • seminiferous tubules exhibit numerous vacuoles, sloughing of germ cells into the lumen, and mislocalized germ cells

small seminiferous tubules ( J:122018 )

♂ • seminiferous tubule lumens tend to be small or absent, possibly due to failure of spermatid maturation and spermiation

arrest of spermiogenesis ( J:122018 )

♂ • differentiation of postmeiotic spermatids into spermatozoa is inhibited

abnormal sperm physiology ( J:82546 )

♂ • testicular sperm are highly sensitive to sonication, showing ~65% reduction in numbers after treatment

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:122018 )

♂ • seminiferous tubules exhibit numerous vacuoles, sloughing of germ cells into the lumen, and mislocalized germ cells

small seminiferous tubules ( J:122018 )

♂ • seminiferous tubule lumens tend to be small or absent, possibly due to failure of spermatid maturation and spermiation

embryo

abnormal preimplantation embryo development ( J:82546 )

• when intracytoplasmic sperm injection is performed, testicular sperm are unable to support development to the blastocyst stage, resulting in arrested development either before or just after compaction

• embryos fertilized with testicular sperm often appear to stall during the compaction process, with some blastomeres remaining uncompacted

• those few that proceed to form blastoceol cavities do so poorly, often forming misshapen cavities that resemble parthenogenetic embryos

cellular

abnormal sperm flagellum morphology ( J:122018 )

♂ • testicular sperm exhibit a variety of tail defects, suggesting a role for the PP1gamma2 isoform (whose expression increases significantly during spermiogenesis in wild-type testes) in sperm tail morphogenesis

abnormal outer dense fiber morphology ( J:122018 )

♂ • in the principal sperm piece, outer dense fibers (ODFs) appear disorganized

♂ • many extra ODF florets (total of 13) are observed throughout the sperm flagella

abnormal sperm midpiece morphology ( J:122018 )

♂ • testicular sperm midpieces exhibit disorganized mitochondrial sheaths or appear thinner than the principal pieces due to absence of mitochondrial sheaths

abnormal sperm mitochondrial sheath morphology ( J:122018 )

♂ • mitochondrial sheaths of elongating spermatids and testicular spermatozoa appear disorganized and do not form the tightly packed helical structures found in wild-type sperm

absent sperm mitochondrial sheath ( J:122018 )

♂ • in some cases, mitochondrial sheaths are absent in testicular sperm

abnormal sperm principal piece morphology ( J:122018 )

♂ • in the principal sperm piece, outer dense fibers (ODFs) appear disorganized

♂ • many extra ODF florets (total of 13) are observed throughout the sperm flagella

abnormal sperm fibrous sheath morphology ( J:122018 )

♂ • a mild developmental abnormality of the fibrous sheath (FS) is observed, specifically in the morphology of its longitudinal columns, consistent with reduced or absent FS-specific protein expression

multiflagellated sperm ( J:82546 )

♂ • testicular sperm often display multiple tails

oligozoospermia ( J:82546 , J:122018 )

♂ • male homozygotes are severely oligospermic; most homozygotes do not shed any sperm into the epididymis (J:82546)

♂ • epididymides are virtually devoid of sperm; only immature germ cells, including round spermatids and, occasionally, pachytene spermatocytes, are observed (J:122018)

♂ • testicular sperm are present, although at reduced numbers relative to those found in wild-type testes (J:122018)

abnormal sperm head morphology ( J:82546 , J:122018 )

♂ • testicular sperm typically exhibit misshapen heads (J:82546)

♂ • all testicular sperm exhibit a range of aberrant head shapes, from round to oblong (J:122018)

globozoospermia ( J:122018 )

♂

pinhead sperm ( J:122018 )

♂

abnormal spermatid morphology ( J:122018 )

♂ • the number of mature elongated spermatids is severely reduced near the lumen of seminiferous tubules

♂ • degeneration of condensing spermatids, characterized by fragmentation of tail structures and the presence of numerous vacuoles in the cytoplasm of elongated spermatids, is observed

♂ • in contrast, the number of round spermatids is relatively normal in some seminiferous tubules