Phenotypes associated with this allele

• Allele Symbol: Gpx4^tm4Marc
• Allele Name: targeted mutation 4, Marcus Conrad
• Allele ID: MGI:5769979
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gpx4^tm4Marc/Gpx4^tm4Marc	involves: 129S6/SvEvTac * C57BL/6J	MGI:5803863
ht2	Gpx4^tm4Marc/Gpx4^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:5803864

Genotype
MGI:5803863

hm1

• Allelic Composition: Gpx4^tm4Marc/Gpx4^tm4Marc
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

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

Gpx4^tm4Marc/Gpx4^tm4Marc embryos show resorptions and severe abnormalities of embryonic and extraembryonic structures

mortality/aging

embryonic lethality between implantation and placentation, complete penetrance ( J:225651 )

• homozygous embryos die at E7.5-E8.5

• an increased number of resorptions and empty decidua, but no viable embryos, are noted at E9.5

embryo

abnormal germ layer development ( J:225651 )

• a clear distinction of the three germinal layers is not possible

failure to gastrulate ( J:225651 )

abnormal embryonic tissue morphology ( J:225651 )

• severe abnormalities in embryonic structures

abnormal extraembryonic tissue morphology ( J:225651 )

• severe abnormalities in extraembryonic structures

reproductive system

empty decidua capsularis ( J:225651 )

• empty decidua at E9.5

Genotype
MGI:5803864

ht2

• Allelic Composition: Gpx4^tm4Marc/Gpx4⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

Severe morphological alterations in the midpiece of developing and mature sperm in Gpx4^tm4Marc/Gpx4⁺ mice

reproductive system

abnormal sperm midpiece morphology ( J:225651 )

♂ • immunocytochemical staining of whole-mount spermatozoa revealed elevated Gpx4 expression particularly in the midpiece of isolated spermatozoa

♂ • many severe morphological defecs are observed in the midpiece and midpiece-principal piece junction of developing and mature sperm

♂ • aberrations include bends mainly at the midpiece-principal piece junction, irregularly aligned mitochondria, and protrusions of outer dense fibers

increased sperm mitochondrial size ( J:225651 )

♂ • late stage spermatids and epididymal spermatozoa exhibit swollen mitochondria surrounding the axoneme

kinked sperm flagellum ( J:225651 )

♂ • bends mainly at the midpiece-principal piece junction

abnormal sperm head morphology ( J:225651 )

♂ • immunocytochemical staining of whole-mount spermatozoa revealed elevated Gpx4 expression in the head of isolated spermatozoa

decreased litter size ( J:225651 )

♂ • heterozygous males yield litter sizes ranging from 2 to 10 pups per litter relative to 1 to 11 pups per litter in wild-type controls

reduced male fertility ( J:225651 )

♂ • male heterozygotes are subfertile in conventional breeding and in vitro fertilization assays

♂ • test breeding of heterozygous males with wild-type C57BL/6J females yielded 11 litters with a total number of 70 offspring whereas breeding of wild-type males yielded 17 litters with a total number of 119 offspring

impaired fertilization ( J:225651 )

♂ • in vitro fertilization assays using heterozygous mutant sperm and wild-type oocytes revealed a significant reduction in the number of zygotes (pro-nuclei stage embryos) and developed blastocysts (16 zygotes; 2 blastocysts) relative to wild-type controls (105 zygotes; 20 blastocysts)

decreased fertilization frequency ( J:225651 )

♂ • in vitro fertilization assays using heterozygous mutant sperm and wild-type oocytes revealed a significant reduction in the number of zygotes (pro-nuclei stage embryos) and developed blastocysts (16 zygotes; 2 blastocysts) relative to wild-type controls (105 zygotes; 20 blastocysts)

abnormal sperm physiology ( J:225651 )

♂ • sperm isolated from the cauda epididymis exhibit higher levels of free reduced thiols than wild-type sperm

abnormal sperm motility ( J:225651 )

♂ • spermatozoa from heterozygous males exhibit a decrease in overall sperm progressivity

♂ • however, total sperm concentration and motility are normal

cellular

abnormal sperm midpiece morphology ( J:225651 )

♂ • immunocytochemical staining of whole-mount spermatozoa revealed elevated Gpx4 expression particularly in the midpiece of isolated spermatozoa

♂ • many severe morphological defecs are observed in the midpiece and midpiece-principal piece junction of developing and mature sperm

♂ • aberrations include bends mainly at the midpiece-principal piece junction, irregularly aligned mitochondria, and protrusions of outer dense fibers

increased sperm mitochondrial size ( J:225651 )

♂ • late stage spermatids and epididymal spermatozoa exhibit swollen mitochondria surrounding the axoneme

kinked sperm flagellum ( J:225651 )

♂ • bends mainly at the midpiece-principal piece junction

abnormal sperm head morphology ( J:225651 )

♂ • immunocytochemical staining of whole-mount spermatozoa revealed elevated Gpx4 expression in the head of isolated spermatozoa

abnormal sperm motility ( J:225651 )

♂ • spermatozoa from heterozygous males exhibit a decrease in overall sperm progressivity

♂ • however, total sperm concentration and motility are normal