Phenotypes associated with this allele

• Allele Symbol: Ddx4^{tm1.1(cre)Dcp}
• Allele Name: targeted mutation 1.1, David C Page
• Allele ID: MGI:5554579
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ddx4^tm1.1(cre)Dcp/Ddx4^+ Rb1^tm3Tyj/Rb1^tm3Tyj	involves: 129S4/SvJae * C57BL/6	MGI:5554595
cn2	Gcna^tm1.1Dcp/Y Ddx4^tm1.1(cre)Dcp/Ddx4^+	involves: C57BL/6 * C57BL/6N	MGI:8250391
cn3	Gcna^tm1.1Dcp/Gcna^tm1.1Dcp Ddx4^tm1.1(cre)Dcp/Ddx4^+	involves: C57BL/6 * C57BL/6N	MGI:8250392

Genotype
MGI:5554595

cn1

• Allelic Composition: Ddx4^{tm1.1(cre)Dcp}/Ddx4⁺; Rb1^tm3Tyj/Rb1^tm3Tyj
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

reproductive system

small testis ( J:198777 )

♂ • testes of mature males are small relative to controls

decreased testis weight ( J:198777 )

♂ • testis weight increases similar to controls in initial 3-4 weeks of age, then begins to decline and remains low in adult males

abnormal spermatogenesis ( J:198777 )

♂

abnormal fertility/fecundity ( J:198777 )

♂ • when males are housed with wild-type females for 21 weeks from 4 weeks of age, each animal only sires one litter (litter is slightly decreased in size versus wild-type males); control males sire 4-6 litters over 21 week period

male infertility ( J:198777 )

♂ • by 2 months of age, males are sterile

endocrine/exocrine glands

small testis ( J:198777 )

♂ • testes of mature males are small relative to controls

decreased testis weight ( J:198777 )

♂ • testis weight increases similar to controls in initial 3-4 weeks of age, then begins to decline and remains low in adult males

Genotype
MGI:8250391

cn2

• Allelic Composition: Gcna^tm1.1Dcp/Y; Ddx4^{tm1.1(cre)Dcp}/Ddx4⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N

reproductive system

oligozoospermia ( J:235710 )

♂ • epididymal ducts are nearly devoid of sperm in the lumen

abnormal sperm head morphology ( J:284005 )

♂ • sperm exhibit an array of abnormal head shapes consistent with failure to execute proper sperm DNA topological rearrangements necessary for full compaction

absent chiasmata formation ( J:284005 )

♂ • diplotene spermatocytes show prematurely separated bivalents, indicating lack of chiasmata

abnormal chromosomal synapsis ( J:284005 )

♂ • 9.2% of pachytene spermatocytes show mild asynapsis of one or a few chromosomes accompanied by DNA damage, as detected by gamma-H2AX staining, relative to 0.9% of wild-type nuclei

♂ • despite aberrant chromatin condensation in all leptotene cells, 82% of pachytene and 89% of diplotene nuclei show normal synapsis and DNA damage resolution relative to 97% and 100% of wild-type nuclei, respectively

abnormal male meiosis ( J:284005 )

♂ • during prophase I of meiosis, all leptotene spermatocytes (stage VII-IX) show marked premature chromatin condensation; chromatin is largely detached from the nuclear membrane, occupying only a small fraction of the nucleus

♂ • zygotene (X-XI) spermatocytes exhibit more compact chromatin than wild-type cells; however, by pachytene, nuclei recover a nearly wild-type histological appearance

♂ • crossover analysis in pachytene spermatocyte spreads immunostained for SYCP3 (a component of the synaptonemal complex) and MLH1 (a marker for meiotic recombination events) shows significantly fewer MLH1 foci per nucleus (21 versus 26 in wild-type nuclei), an increased % of bivalents with no MLH1 focus, and a decreased % of bivalents with two MLH1 foci

♂ • pachytene bivalents exhibit significantly less crossover interference for chromosomes 14-19 (8.498 versus 11.274 in wild-type) and chromosomes 11-13 (9.479 versus in 11.037 wild-type), as determined by the gamma shape parameter

♂ • 79% of diplotene nuclei have at least one univalent chromosome pair versus 32.5% in wild-type nuclei

♂ • abnormal diplotene spermatocytes show an average of 4 sets of univalents per nucleus versus 1.8 in wild-type nuclei; of the nuclei with at least one set of univalents, none affect only sex chromosomes, 36% affect only autosomes, and 64% affect both autosomes and sex chromosomes versus 21%, 43%, and 36%, respectively, in wild-type nuclei

♂ • overall meiotic phenotypes (persistent DNA damage, decreased crossovers and crossover interference, and chromatin condensation defects) are consistent with an inability to process/resolve DNA-protein crosslinks (DPCs)

male infertility ( J:235710 )

♂ • 10 of 11 males tested fail to sire offspring

reduced male fertility ( J:235710 )

♂ • male mice exhibit severe subfertility; most males are sterile

cellular

oligozoospermia ( J:235710 )

♂ • epididymal ducts are nearly devoid of sperm in the lumen

abnormal sperm head morphology ( J:284005 )

♂ • sperm exhibit an array of abnormal head shapes consistent with failure to execute proper sperm DNA topological rearrangements necessary for full compaction

absent chiasmata formation ( J:284005 )

♂ • diplotene spermatocytes show prematurely separated bivalents, indicating lack of chiasmata

abnormal chromosomal synapsis ( J:284005 )

♂ • 9.2% of pachytene spermatocytes show mild asynapsis of one or a few chromosomes accompanied by DNA damage, as detected by gamma-H2AX staining, relative to 0.9% of wild-type nuclei

♂ • despite aberrant chromatin condensation in all leptotene cells, 82% of pachytene and 89% of diplotene nuclei show normal synapsis and DNA damage resolution relative to 97% and 100% of wild-type nuclei, respectively

abnormal male meiosis ( J:284005 )

♂ • during prophase I of meiosis, all leptotene spermatocytes (stage VII-IX) show marked premature chromatin condensation; chromatin is largely detached from the nuclear membrane, occupying only a small fraction of the nucleus

♂ • zygotene (X-XI) spermatocytes exhibit more compact chromatin than wild-type cells; however, by pachytene, nuclei recover a nearly wild-type histological appearance

♂ • crossover analysis in pachytene spermatocyte spreads immunostained for SYCP3 (a component of the synaptonemal complex) and MLH1 (a marker for meiotic recombination events) shows significantly fewer MLH1 foci per nucleus (21 versus 26 in wild-type nuclei), an increased % of bivalents with no MLH1 focus, and a decreased % of bivalents with two MLH1 foci

♂ • pachytene bivalents exhibit significantly less crossover interference for chromosomes 14-19 (8.498 versus 11.274 in wild-type) and chromosomes 11-13 (9.479 versus in 11.037 wild-type), as determined by the gamma shape parameter

♂ • 79% of diplotene nuclei have at least one univalent chromosome pair versus 32.5% in wild-type nuclei

♂ • abnormal diplotene spermatocytes show an average of 4 sets of univalents per nucleus versus 1.8 in wild-type nuclei; of the nuclei with at least one set of univalents, none affect only sex chromosomes, 36% affect only autosomes, and 64% affect both autosomes and sex chromosomes versus 21%, 43%, and 36%, respectively, in wild-type nuclei

♂ • overall meiotic phenotypes (persistent DNA damage, decreased crossovers and crossover interference, and chromatin condensation defects) are consistent with an inability to process/resolve DNA-protein crosslinks (DPCs)

abnormal DNA repair ( J:284005 )

♂ • overall, 9.2% of pachytene spermatocytes exhibit mild asynapsis and DNA damage, as detected by gamma-H2AX staining

♂ • nuclei with gamma-H2AX anomalies show aberrant BRCA1 and ATR localization (proteins involved in the DNA damage response), indicating that damage repair and synapsis are interdependent

♂ • 7.7% of pachytene and 6.5% of diplotene spermatocytes retain gamma-H2AX and ATR proteins throughout the nucleus even where synapsis proceeds normally, indicating persistent DNA damage

♂ • male meiotic phenotypes are consistent with buildup of topoisomerase 2 (TOP2) DNA-protein crosslinks (DPCs)

chromosomal instability ( J:284005 )

♂ • spermatocytes show defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects

homeostasis/metabolism

abnormal DNA repair ( J:284005 )

♂ • overall, 9.2% of pachytene spermatocytes exhibit mild asynapsis and DNA damage, as detected by gamma-H2AX staining

♂ • nuclei with gamma-H2AX anomalies show aberrant BRCA1 and ATR localization (proteins involved in the DNA damage response), indicating that damage repair and synapsis are interdependent

♂ • 7.7% of pachytene and 6.5% of diplotene spermatocytes retain gamma-H2AX and ATR proteins throughout the nucleus even where synapsis proceeds normally, indicating persistent DNA damage

♂ • male meiotic phenotypes are consistent with buildup of topoisomerase 2 (TOP2) DNA-protein crosslinks (DPCs)

Genotype
MGI:8250392

cn3

• Allelic Composition: Gcna^tm1.1Dcp/Gcna^tm1.1Dcp; Ddx4^{tm1.1(cre)Dcp}/Ddx4⁺
• Genetic Background: involves: C57BL/6 * C57BL/6N

reproductive system

reproductive system phenotype ( J:235710 )

♀N • female mice are fertile