Phenotypes associated with this allele

• Allele Symbol: Ythdf2^{tm1c(KOMP)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:7444511
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ythdf2^tm1c(KOMP)Wtsi/Ythdf2^tm1c(KOMP)Wtsi Stra8^em1(GFP/cre)Smoc/Stra8^+	involves: C57BL/6N	MGI:7860771
cn2	Ythdf2^tm1c(KOMP)Wtsi/Ythdf2^tm1c(KOMP)Wtsi Tg(Ddx4-cre)1Dcas/0	involves: C57BL/6N * FVB	MGI:7860765

Genotype
MGI:7860771

cn1

• Allelic Composition: Ythdf2^{tm1c(KOMP)Wtsi}/Ythdf2^{tm1c(KOMP)Wtsi}; Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
• Genetic Background: involves: C57BL/6N

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

reproductive system

reproductive system phenotype ( J:324152 )

♂N • adult male mice show normal gross testis morphology and testis/body weight ratio relative to wild-type controls

oligozoospermia ( J:324152 )

♂ • adult males exhibit a significantly lower cauda epididymal sperm count than wild-type controls

teratozoospermia ( J:324152 )

♂ • about 50% of cauda epididymal sperm are deformed with various structural anomalies

increased male germ cell apoptosis ( J:324152 )

♂ • adult testes show a significant increase in TUNEL+ apoptotic sperm

decreased sperm progressive motility ( J:324152 )

♂ • sperm progressive motility is markedly impaired

asthenozoospermia ( J:324152 )

♂ • sperm motility is markedly impaired

impaired fertilization ( J:324152 )

♂ • cauda epididymal sperm from adult males fail to fertilize wild-type oocytes in IVF assays

cellular

oligozoospermia ( J:324152 )

♂ • adult males exhibit a significantly lower cauda epididymal sperm count than wild-type controls

teratozoospermia ( J:324152 )

♂ • about 50% of cauda epididymal sperm are deformed with various structural anomalies

increased male germ cell apoptosis ( J:324152 )

♂ • adult testes show a significant increase in TUNEL+ apoptotic sperm

decreased sperm progressive motility ( J:324152 )

♂ • sperm progressive motility is markedly impaired

asthenozoospermia ( J:324152 )

♂ • sperm motility is markedly impaired

Genotype
MGI:7860765

cn2

• Allelic Composition: Ythdf2^{tm1c(KOMP)Wtsi}/Ythdf2^{tm1c(KOMP)Wtsi}; Tg(Ddx4-cre)1Dcas/0
• Genetic Background: involves: C57BL/6N * FVB

reproductive system

reproductive system phenotype ( J:324152 )

♂N • adult male mice show normal gross testis morphology and testis/body weight ratio relative to wild-type controls

increased male germ cell apoptosis ( J:324152 )

♂ • adult testes show a significant increase in TUNEL+ apoptotic cells; the apoptosis signal is primarily detected in elongated spermatids

decreased sperm progressive motility ( J:324152 )

♂ • sperm progressive motility is markedly impaired

asthenozoospermia ( J:324152 )

♂ • sperm motility is markedly impaired

abnormal spermatogenesis ( J:324152 )

♂ • during transition from differentiated spermatogonia to pachytene spermatocytes, most N6-methyladenosine (m⁶A)-modified RNA targets bound by YTHDF2 are found to persist in pachytene spermatocytes; these delayed mRNAs are primarily associated with pathways involved in transcriptional regulation, subsequently disturbing the transcriptome of both round spermatids and elongated spermatids

♂ • however, early stages of spermatogenesis are normal with no apparent defects in meiosis; adult testes show no differences in the % of leptotene, zygotene, pachytene and diplotene spermatocytes or in the number of PLZF+ spermatogonia relative to wild-type controls

oligozoospermia ( J:324152 )

♂ • adult males exhibit a significantly lower cauda epididymal sperm count than wild-type controls

teratozoospermia ( J:324152 )

♂ • more than 40% of cauda epididymal sperm are deformed with various structural anomalies

male infertility ( J:324152 )

♂ • adult males fail to produce offspring when mated with wild-type females

♂ • however, copulatory plugs are observed

impaired fertilization ( J:324152 )

♂ • cauda epididymal sperm from adult males fail to fertilize wild-type oocytes in IVF assays

♂ • however, after intracytoplasmic sperm injection (ICSI), fertilized eggs are able to develop to the blastocyst stage normally

cellular

oligozoospermia ( J:324152 )

♂ • adult males exhibit a significantly lower cauda epididymal sperm count than wild-type controls

teratozoospermia ( J:324152 )

♂ • more than 40% of cauda epididymal sperm are deformed with various structural anomalies

increased male germ cell apoptosis ( J:324152 )

♂ • adult testes show a significant increase in TUNEL+ apoptotic cells; the apoptosis signal is primarily detected in elongated spermatids

decreased sperm progressive motility ( J:324152 )

♂ • sperm progressive motility is markedly impaired

asthenozoospermia ( J:324152 )

♂ • sperm motility is markedly impaired

homeostasis/metabolism

abnormal metabolism ( J:324152 )

♂ • during transition from differentiated spermatogonia to pachytene spermatocytes, most m⁶A-modified YTHDF2 targets that are normally degraded in wild-type germ cells are found to persist in pachytene spermatocytes, leading to delayed degradation

♂ • persistent mRNAs are primarily associated with pathways involved in transcriptional regulation, subsequently disturbing the transcriptome of both round spermatids and elongated spermatids