All Phenotypes Mettl3<em1Chhe> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mettl3^em1Chhe/Mettl3^em1Chhe Mettl14^em1Chhe/Mettl14^em1Chhe Stra8^{em1(GFP/cre)Smoc}/Stra8⁺	involves: C57BL/6J	MGI:6681853
cn2	Mettl3^em1Chhe/Mettl3^em1Chhe Stra8^{em1(GFP/cre)Smoc}/Stra8⁺	involves: C57BL/6J	MGI:6681851
cn3	Mettl3^em1Chhe/Mettl3^em1Chhe Mettl14^em1Chhe/Mettl14^em1Chhe Tg(Ddx4-cre)1Dcas/0	involves: C57BL/6J * FVB	MGI:6681848
cn4	Mettl3^em1Chhe/Mettl3^em1Chhe Tg(Ddx4-cre)1Dcas/0	involves: C57BL/6J * FVB	MGI:6681844

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

reproductive system

oligozoospermia ( J:250428 )

• caudal epididymal sperm count is only ~2% of that in control mice

teratozoospermia ( J:250428 )

abnormal sperm head morphology ( J:250428 )

• >80% of caudal epididymal sperm exhibit abnormal heads

• elongated spermatids show abnormal head morphologies at epithelial stages I-VIII

abnormal spermatid morphology ( J:250428 )

• elongated spermatids show abnormal head morphologies and their number is severely decreased from step 13 to step 16 at epithelial stages I-VIII

decreased sperm progressive motility ( J:250428 )

• progressive motility of caudal epididymal sperm is severely reduced at 2 months of age

asthenozoospermia ( J:250428 )

• CASA analysis revealed that total motility of caudal epididymal sperm is severely reduced at 2 months of age, indicating defects in sperm flagella

abnormal seminiferous tubule morphology ( J:250428 )

• seminiferous tubules contain very few mature spermatozoa

• however, no detectable abnormalities are observed in germ cells up to step 12 of elongating spermatids

small testis ( J:250428 )

• adult testes are significantly smaller than those in controls

decreased testis weight ( J:250428 )

• adult testis/body weight (%) is significantly lower than that in controls

arrest of spermiogenesis ( J:250428 )

• spermatid differentiation is blocked in late stages of spermiogenesis

• unexpectedly, male meiosis is normal

cellular

oligozoospermia ( J:250428 )

• caudal epididymal sperm count is only ~2% of that in control mice

teratozoospermia ( J:250428 )

abnormal sperm head morphology ( J:250428 )

• >80% of caudal epididymal sperm exhibit abnormal heads

• elongated spermatids show abnormal head morphologies at epithelial stages I-VIII

abnormal spermatid morphology ( J:250428 )

• elongated spermatids show abnormal head morphologies and their number is severely decreased from step 13 to step 16 at epithelial stages I-VIII

decreased sperm progressive motility ( J:250428 )

• progressive motility of caudal epididymal sperm is severely reduced at 2 months of age

asthenozoospermia ( J:250428 )

• CASA analysis revealed that total motility of caudal epididymal sperm is severely reduced at 2 months of age, indicating defects in sperm flagella

abnormal epigenetic regulation of gene expression ( J:250428 )

• N⁶-methyladenosine (m⁶A) levels in spermatids of double knockout mice are significantly lower than those in single Mettl3^em1Chhe or Mettl14^em1Chhe knockouts

• however, no significant differences in m⁶A levels are noted between double knockout and single knockout spermatocytes

abnormal translation ( J:250428 )

• spermatids from double mutant mice show impaired translation of haploid-specific genes that are essential for spermiogenesis

homeostasis/metabolism

abnormal translation ( J:250428 )

• spermatids from double mutant mice show impaired translation of haploid-specific genes that are essential for spermiogenesis

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:250428 )

• seminiferous tubules contain very few mature spermatozoa

• however, no detectable abnormalities are observed in germ cells up to step 12 of elongating spermatids

small testis ( J:250428 )

• adult testes are significantly smaller than those in controls

decreased testis weight ( J:250428 )

• adult testis/body weight (%) is significantly lower than that in controls

Allelic Composition	Mettl3^em1Chhe/Mettl3^em1Chhe Stra8^{em1(GFP/cre)Smoc}/Stra8⁺
Genetic Background	involves: C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl3^em1Chhe mutation (0 available); any Mettl3 mutation (39 available)
Stra8^{em1(GFP/cre)Smoc} mutation (0 available); any Stra8 mutation (35 available)

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

reproductive system

reproductive system phenotype ( J:250428 )

N	• male mice are fertile and exhibit normal spermatogenesis with no detectable defects in meiosis or spermiogenesis

cellular

abnormal epigenetic regulation of gene expression ( J:250428 )

• N⁶-methyladenosine (m⁶A) levels are reduced by 55-65% in pachytene spermatocytes and by 45% in round spermatids relative to controls

Allelic Composition	Mettl3^em1Chhe/Mettl3^em1Chhe Mettl14^em1Chhe/Mettl14^em1Chhe Tg(Ddx4-cre)1Dcas/0
Genetic Background	involves: C57BL/6J * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl14^em1Chhe mutation (0 available); any Mettl14 mutation (36 available)
Mettl3^em1Chhe mutation (0 available); any Mettl3 mutation (39 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)

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

reproductive system

abnormal spermatogonia morphology ( J:250428 )

• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or PLZF+ undifferentiated spermatogonia are detected at 4 weeks

decreased male germ cell number ( J:250428 )

• double knockout mice exhibit progressive loss of spermatogonial stem cells, similar to single Mettl3^em1Chhe or Mettl14^em1Chhe knockouts

cellular

abnormal spermatogonia morphology ( J:250428 )

• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or PLZF+ undifferentiated spermatogonia are detected at 4 weeks

decreased male germ cell number ( J:250428 )

• double knockout mice exhibit progressive loss of spermatogonial stem cells, similar to single Mettl3^em1Chhe or Mettl14^em1Chhe knockouts

Allelic Composition	Mettl3^em1Chhe/Mettl3^em1Chhe Tg(Ddx4-cre)1Dcas/0
Genetic Background	involves: C57BL/6J * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mettl3^em1Chhe mutation (0 available); any Mettl3 mutation (39 available)
Tg(Ddx4-cre)1Dcas mutation (2 available)

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

reproductive system

abnormal male germ cell morphology ( J:250428 )

• testes show defects in spermatogonial stem cell (SSC) development

• however, testes contain normal numbers of gonocytes at birth

abnormal spermatogonia morphology ( J:250428 )

• the number of undifferentiated spermatogonia (PLZF+ cells) is similar to that in controls up to P5 but significantly decreased by P7

• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks

• however, Aaligned (Aal) spermatogonia (derived from As spermatogonia) remain, indicating that exhaustion of the SSC pool is possibly due to increased SSC proliferation

• little or no difference in apoptosis of PLZF+ spermatogonia is observed at P7

decreased male germ cell number ( J:250428 )

• mice exhibit progressive loss of SSCs, causing germ cell depletion

abnormal male germ cell physiology ( J:250428 )

• at P10, EdU incorporation is significantly increased in GFRalpha1+ Asingle (As) spermatogonia (the most primitive set of spermatogonia), indicating higher proliferation of spermatogonial stem cells (SSCs)

abnormal seminiferous tubule epithelium morphology ( J:250428 )

• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining

small testis ( J:250428 )

• adult testes are smaller than normal

male infertility ( J:250428 )

• males are sterile

cellular

abnormal male germ cell morphology ( J:250428 )

• testes show defects in spermatogonial stem cell (SSC) development

• however, testes contain normal numbers of gonocytes at birth

abnormal spermatogonia morphology ( J:250428 )

• the number of undifferentiated spermatogonia (PLZF+ cells) is similar to that in controls up to P5 but significantly decreased by P7

• no GFRalpha1+ Asingle (As, early stage undifferentiated spermatogonia) or even PLZF+ undifferentiated spermatogonia are detected at 4 weeks

• however, Aaligned (Aal) spermatogonia (derived from As spermatogonia) remain, indicating that exhaustion of the SSC pool is possibly due to increased SSC proliferation

• little or no difference in apoptosis of PLZF+ spermatogonia is observed at P7

decreased male germ cell number ( J:250428 )

• mice exhibit progressive loss of SSCs, causing germ cell depletion

abnormal epigenetic regulation of gene expression ( J:250428 )

• N⁶-methyladenosine (m⁶A) levels are reduced by ~70% in THY1+ undifferentiated spermatogonia

abnormal male germ cell physiology ( J:250428 )

abnormal translation ( J:250428 )

• mRNA m⁶A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

homeostasis/metabolism

abnormal translation ( J:250428 )

• mRNA m⁶A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:250428 )

• by 6 weeks of age, the seminiferous tubule epithelium is completely devoid of any germ cells, with only SOX9+ Sertoli cells remaining

small testis ( J:250428 )

• adult testes are smaller than normal

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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