Phenotypes associated with this allele

• Allele Symbol: Pla2g3^tm1Murm
• Allele Name: targeted mutation 1, Makoto Murakami
• Allele ID: MGI:4461174
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pla2g3^tm1Murm/Pla2g3^tm1Murm	involves: 129S/SvEv * C57BL/6	MGI:5517572
hm2	Pla2g3^tm1Murm/Pla2g3^tm1Murm	involves: 129S/SvEv * C57BL/6J	MGI:4461175
ht3	Pla2g3^tm1Murm/Pla2g3^+	involves: 129S/SvEv * C57BL/6J	MGI:4461176

Genotype
MGI:5517572

hm1

• Allelic Composition: Pla2g3^tm1Murm/Pla2g3^tm1Murm
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

immune system

decreased mast cell degranulation ( J:197334 )

• in mice intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

• reduced IgE-antigen-induced histamine release in mast cells

• lower amount, but not percentage, A23187-induced histamine release from peritoneal mast cells

ear inflammation ( J:197334 )

• following intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis, mice exhibit reduced ear swelling compared with wild-type mice

abnormal mast cell morphology ( J:197334 )

• mast cells contain unusual granules that are small and irregular in size indicating immature mast cells compared to in wild-type mice

• peritoneal mast cells contain smaller and more irregular granules than in wild-type cells

abnormal mast cell differentiation ( J:197334 )

• mast cells contain unusual granules that are small and irregular in size indicating immature mast cells compared to in wild-type mice

• transfer experiments confirmed cell autonomous defects in mast cell maturation and activation

• mast cells exhibit impaired maturation in culture

decreased susceptibility to type I hypersensitivity reaction ( J:197334 )

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

• following passive systemic anaphylaxis induced by C48/C80 challenge, mice exhibit mild edema compared with wild-type mice

• following intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis, mice exhibit lower local anaphylaxis with reduced ear swelling and mast cell degranulation compared with wild-type mice

• however, anti-ovalbumin IgE levels are normal in mice intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis

homeostasis/metabolism

abnormal body temperature ( J:197334 )

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

edema ( J:197334 )

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

• following passive systemic anaphylaxis induced by C48/C80 challenge, mice exhibit mild edema compared with wild-type mice

hearing/vestibular/ear

ear inflammation ( J:197334 )

• following intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis, mice exhibit reduced ear swelling compared with wild-type mice

cellular

abnormal mast cell differentiation ( J:197334 )

• mast cells contain unusual granules that are small and irregular in size indicating immature mast cells compared to in wild-type mice

• transfer experiments confirmed cell autonomous defects in mast cell maturation and activation

• mast cells exhibit impaired maturation in culture

decreased mast cell degranulation ( J:197334 )

• in mice intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

• reduced IgE-antigen-induced histamine release in mast cells

• lower amount, but not percentage, A23187-induced histamine release from peritoneal mast cells

hematopoietic system

decreased mast cell degranulation ( J:197334 )

• in mice intraperitoneally immunized with alum-adsorbed ovalbumin then intradermal injection of ovalbumin to elicit active cutaneous anaphylaxis

• following passive systemic anaphylaxis induced by IgE antigen challenge, mice exhibit mild increase in plasma histamine, temporary decrease in rectal temperature and edema compared with wild-type mice

• reduced IgE-antigen-induced histamine release in mast cells

• lower amount, but not percentage, A23187-induced histamine release from peritoneal mast cells

abnormal mast cell morphology ( J:197334 )

• mast cells contain unusual granules that are small and irregular in size indicating immature mast cells compared to in wild-type mice

• peritoneal mast cells contain smaller and more irregular granules than in wild-type cells

abnormal mast cell differentiation ( J:197334 )

• mast cells contain unusual granules that are small and irregular in size indicating immature mast cells compared to in wild-type mice

• transfer experiments confirmed cell autonomous defects in mast cell maturation and activation

• mast cells exhibit impaired maturation in culture

Genotype
MGI:4461175

hm2

• Allelic Composition: Pla2g3^tm1Murm/Pla2g3^tm1Murm
• Genetic Background: involves: 129S/SvEv * C57BL/6J

Sperm dysfunction of Pla2g3^tm1Murm/Pla2g3^tm1Murm mice

mortality/aging

embryonic lethality before implantation, complete penetrance ( J:161462 )

• increased dead embryos at 24 hours after in vitro fertilization (IVF) assay

embryo

abnormal preimplantation embryo development ( J:161462 )

• delayed or stopped egg progression to the morula stage after in vitro fertilization (IVF) assay

• fewer eggs that have fused with the mutant sperm progress beyond the 2- or 4-cell stage

• lower proportion of eggs that develop into morulae relative to those at the 2-cell stage

reproductive system

abnormal outer dense fiber morphology ( J:161462 )

♂ • disorganized outer dense fibers

♂ • outer dense fibers are mislocated outside the mitochondrial lines

abnormal sperm axoneme morphology ( J:161462 )

♂ • marked ultrastructural structural defects in cauda epididymal spermatozoa

♂ • incomplete axonemal doublets

♂ • loss of one doublet or half of the axonemal complex

♂ • lack the central pair of microtubules

♂ • double axonemes in the principal piece and in the midpiece of the flagellum

♂ • abnormal morphology is rare in the testis and the caput epididymidis

absent sperm axonemal central pair ( J:161462 )

♂ • lack the central pair of microtubules

increased sperm mitochondrial size ( J:161462 )

• unequally sized and swollen mitochondria in spermatozoa

disorganized sperm mitochondrial sheath ( J:161462 )

♂ • disorganized middle piece of spermatozoa with unequally sized and swollen mitochondria

coiled sperm flagellum ( J:161462 )

♂

kinked sperm flagellum ( J:161462 )

♂

biflagellated sperm ( J:161462 )

♂ • duplicate tails

abnormal acrosome morphology ( J:161462 )

♂ • expanded acrosomes

♂ • vacuoles beneath the acrosome cap

globozoospermia ( J:161462 )

♂ • sperm frequently possess round-shaped

♂ • nearly half of the cauda epididymal spermatozoa had abnormal heads

abnormal caput epididymis morphology ( J:161462 )

♂ • a trend toward accumulation of larger cytoplasmic vesicles in the caput epithelium

decreased litter size ( J:161462 )

• smaller litter for homozygous mutant male mice compared with wild-type

• after backcrossing to a C57BL/6J background for several generations, mutant males do not produce any pups

• normal histology of the testis and epididymis

• normal serum testosterone levels

• normal sperm counts

decreased fertilization frequency ( J:161462 )

• increased unfertilized eggs at 24 hours after in vitro fertilization (IVF) assay

• severely reduced ability to fertilize zona pellucida (ZP)-intact eggs (10% of the eggs) in an in vitro fertilization assay, compared with wild-type (50% of the eggs)

• spermatozoa from the mutant mice are able to fertilize eggs normally once the ZP has been removed

impaired binding of sperm to zona pellucida ( J:161462 )

♂ • impaired binding of the mutant sperm to the egg ZP

♂ • greatly reduced average numbers of sperm associated with the egg surface

abnormal male reproductive system physiology ( J:161462 )

♂ • reduced phospholipase A2 (PLA2) enzymatic activity in cauda epididymal fluid

reduced male fertility ( J:161462 )

♂ • smaller litter for homozygous mutant male mice compared with wild-type

♂ • after backcrossing to a C57BL/6J background for several generations, mutant males do not produce any pups

abnormal sperm physiology ( J:161462 )

♂ • markedly lower level of pyruvate kinase (ATP) level in mutant spermatozoa

♂ • reduced inducible tyrosine phosphorylation in spermatozoa after 60 and 90 minutes incubation

decreased activated sperm motility ( J:161462 )

♂ • reduced motile (27%), compared with wild type (81%)

♂ • spermatozoa accumulate in the lower part of the uterus, not reaching the upper part of the uterus and the oviduct

decreased sperm progressive motility ( J:161462 )

• flagellar motion of sperm from is sluggish and rarely results in forward movement

• markedly reduced straight-line and curvilinear velocities and amplitude in spermatozoa

homeostasis/metabolism

abnormal phospholipid level ( J:161462 )

• markedly different fatty acyl composition of phosphatidylcholine (PC), a major phospholipid in spermatozoa in cauda epididymal spermatozoa

cellular

abnormal outer dense fiber morphology ( J:161462 )

♂ • disorganized outer dense fibers

♂ • outer dense fibers are mislocated outside the mitochondrial lines

abnormal sperm axoneme morphology ( J:161462 )

♂ • marked ultrastructural structural defects in cauda epididymal spermatozoa

♂ • incomplete axonemal doublets

♂ • loss of one doublet or half of the axonemal complex

♂ • lack the central pair of microtubules

♂ • double axonemes in the principal piece and in the midpiece of the flagellum

♂ • abnormal morphology is rare in the testis and the caput epididymidis

absent sperm axonemal central pair ( J:161462 )

♂ • lack the central pair of microtubules

increased sperm mitochondrial size ( J:161462 )

• unequally sized and swollen mitochondria in spermatozoa

disorganized sperm mitochondrial sheath ( J:161462 )

♂ • disorganized middle piece of spermatozoa with unequally sized and swollen mitochondria

coiled sperm flagellum ( J:161462 )

♂

kinked sperm flagellum ( J:161462 )

♂

biflagellated sperm ( J:161462 )

♂ • duplicate tails

abnormal acrosome morphology ( J:161462 )

♂ • vacuoles beneath the acrosome cap

♂ • expanded acrosomes

globozoospermia ( J:161462 )

♂ • sperm frequently possess round-shaped

♂ • nearly half of the cauda epididymal spermatozoa had abnormal heads

decreased activated sperm motility ( J:161462 )

♂ • reduced motile (27%), compared with wild type (81%)

♂ • spermatozoa accumulate in the lower part of the uterus, not reaching the upper part of the uterus and the oviduct

decreased sperm progressive motility ( J:161462 )

• flagellar motion of sperm from is sluggish and rarely results in forward movement

• markedly reduced straight-line and curvilinear velocities and amplitude in spermatozoa

Genotype
MGI:4461176

ht3

• Allelic Composition: Pla2g3^tm1Murm/Pla2g3⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6J

mortality/aging

embryonic lethality before implantation, complete penetrance ( J:161462 )

• increased dead embryos at 24 hours after in vitro fertilization (IVF) assay

reproductive system

decreased activated sperm motility ( J:161462 )

♂ • reduced motile (43%), compared with wild type (81%)

decreased sperm progressive motility ( J:161462 )

• reduced straight-line and curvilinear velocities and amplitude in spermatozoa

decreased litter size ( J:161462 )

• smaller litter for heterozygous mutant male mice compared with wild-type

reduced male fertility ( J:161462 )

♂ • smaller litter for heterozygous mutant male mice compared with wild-type

decreased fertilization frequency ( J:161462 )

• increased unfertilized eggs at 24 hours after IVF assay

• reduced frequency to fertilize zona pellucida-intact eggs in an IVF assay, compared with wild-type

cellular

decreased activated sperm motility ( J:161462 )

♂ • reduced motile (43%), compared with wild type (81%)

decreased sperm progressive motility ( J:161462 )

• reduced straight-line and curvilinear velocities and amplitude in spermatozoa