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of Dmrt7 heterozygotes produced homozygous mutant progeny of both sexes at the expected frequency (63/264; 23%). Male and female homozygous mutants were viable, grew to adulthood normally, and exhibited normal sexual behavior. Female homozygotes were fertile, produced litters of normal size, and had no obvious ovarian abnormalities as judged by histological analysis (unpublished data). In contrast, Dmrt7 homozygous mutant males were completely infertile and had testes about one-third the weight of those of heterozygous or wild-type adult littermates (Figure 2). To determine when defective testis development begins in Dmrt7 mutants, we compared the testes of wild-type and mutant littermates during the first wave of spermatogenesis. Prior to postnatal day 14 (P14), mutant testes appeared histologically normal and the testis weights were similar to those of heterozygous and wild-type littermates, indicating that spermatogonia and early meiotic germ cells form normally (Figure 2B; unpublished data). Thereafter, the testes of the Dmrt7 mutant mice ceased to grow and the weight difference was significant. Microscopic examination of P21 and P42 Dmrt7 mutant testes revealed that germ cells arrest in pachynema, and later stages of germ cells are largely missing (Figure 2C and 2D). Dmrt7 mutant mice are deficient in postmeiotic spermatids and lack epididymal spermatozoa, although a few cells develop to the round spermatid stage. These meiotic defects are in agreement with a recent preliminary analysis of another Dmrt7 mutation [42]. While some Dmrt7 mutant tubules are highly vacuolated and contain primarily Sertoli cells and spermatogonia, others have abundant primary spermatocytes. In addition, some tubules contain multinucleated cells and cells with darkly stained nuclei that are typical of apoptotic cells (Figure 2D)."}

    2_test

    {"project":"2_test","denotations":[{"id":"17447844-17098235-85805832","span":{"begin":1553,"end":1555},"obj":"17098235"},{"id":"T53612","span":{"begin":1553,"end":1555},"obj":"17098235"}],"text":"Breeding of Dmrt7 heterozygotes produced homozygous mutant progeny of both sexes at the expected frequency (63/264; 23%). Male and female homozygous mutants were viable, grew to adulthood normally, and exhibited normal sexual behavior. Female homozygotes were fertile, produced litters of normal size, and had no obvious ovarian abnormalities as judged by histological analysis (unpublished data). In contrast, Dmrt7 homozygous mutant males were completely infertile and had testes about one-third the weight of those of heterozygous or wild-type adult littermates (Figure 2). To determine when defective testis development begins in Dmrt7 mutants, we compared the testes of wild-type and mutant littermates during the first wave of spermatogenesis. Prior to postnatal day 14 (P14), mutant testes appeared histologically normal and the testis weights were similar to those of heterozygous and wild-type littermates, indicating that spermatogonia and early meiotic germ cells form normally (Figure 2B; unpublished data). Thereafter, the testes of the Dmrt7 mutant mice ceased to grow and the weight difference was significant. Microscopic examination of P21 and P42 Dmrt7 mutant testes revealed that germ cells arrest in pachynema, and later stages of germ cells are largely missing (Figure 2C and 2D). Dmrt7 mutant mice are deficient in postmeiotic spermatids and lack epididymal spermatozoa, although a few cells develop to the round spermatid stage. These meiotic defects are in agreement with a recent preliminary analysis of another Dmrt7 mutation [42]. While some Dmrt7 mutant tubules are highly vacuolated and contain primarily Sertoli cells and spermatogonia, others have abundant primary spermatocytes. In addition, some tubules contain multinucleated cells and cells with darkly stained nuclei that are typical of apoptotic cells (Figure 2D)."}

    craft-ca-core-dev

    {"project":"craft-ca-core-dev","denotations":[{"id":"T9514","span":{"begin":12,"end":17},"obj":"PR:000006549"},{"id":"T9515","span":{"begin":170,"end":174},"obj":"GO:0040007"},{"id":"T9516","span":{"begin":178,"end":187},"obj":"UBERON:0000113"},{"id":"T9517","span":{"begin":219,"end":234},"obj":"GO:0019098"},{"id":"T9518","span":{"begin":321,"end":328},"obj":"UBERON:0000992"},{"id":"T9519","span":{"begin":411,"end":416},"obj":"PR:000006549"},{"id":"T9520","span":{"begin":475,"end":481},"obj":"UBERON:0000473"},{"id":"T9521","span":{"begin":547,"end":552},"obj":"UBERON:0007023"},{"id":"T9522","span":{"begin":605,"end":611},"obj":"UBERON:0000473"},{"id":"T9523","span":{"begin":605,"end":623},"obj":"GO:0008584"},{"id":"T9524","span":{"begin":634,"end":639},"obj":"PR:000006549"},{"id":"T9525","span":{"begin":665,"end":671},"obj":"UBERON:0000473"},{"id":"T9526","span":{"begin":733,"end":748},"obj":"GO:0007283"},{"id":"T9527","span":{"begin":763,"end":768},"obj":"GO:0007567"},{"id":"T9528","span":{"begin":790,"end":796},"obj":"UBERON:0000473"},{"id":"T9529","span":{"begin":836,"end":842},"obj":"UBERON:0000473"},{"id":"T9530","span":{"begin":932,"end":945},"obj":"CL:0000020"},{"id":"T9531","span":{"begin":956,"end":963},"obj":"GO:0007126"},{"id":"T9532","span":{"begin":964,"end":974},"obj":"CL:0000586"},{"id":"T9533","span":{"begin":1036,"end":1042},"obj":"UBERON:0000473"},{"id":"T9534","span":{"begin":1050,"end":1055},"obj":"PR:000006549"},{"id":"T9535","span":{"begin":1063,"end":1067},"obj":"NCBITaxon:10088"},{"id":"T9536","span":{"begin":1078,"end":1082},"obj":"GO:0040007"},{"id":"T9537","span":{"begin":1165,"end":1170},"obj":"PR:000006549"},{"id":"T9538","span":{"begin":1178,"end":1184},"obj":"UBERON:0000473"},{"id":"T9539","span":{"begin":1199,"end":1209},"obj":"CL:0000586"},{"id":"T9540","span":{"begin":1220,"end":1229},"obj":"GO:0000239"},{"id":"T9541","span":{"begin":1241,"end":1250},"obj":"_FRAGMENT"},{"id":"T9542","span":{"begin":1256,"end":1261},"obj":"GO:0022403"},{"id":"T9543","span":{"begin":1251,"end":1261},"obj":"CL:0000586"},{"id":"T9544","span":{"begin":1302,"end":1307},"obj":"PR:000006549"},{"id":"T9545","span":{"begin":1315,"end":1319},"obj":"NCBITaxon:10088"},{"id":"T9546","span":{"begin":1341,"end":1348},"obj":"GO:0007126"},{"id":"T9547","span":{"begin":1349,"end":1359},"obj":"CL:0000018"},{"id":"T9548","span":{"begin":1369,"end":1379},"obj":"UBERON:0001301"},{"id":"T9549","span":{"begin":1380,"end":1391},"obj":"CL:0000019"},{"id":"T9550","span":{"begin":1435,"end":1444},"obj":"CL:0000018"},{"id":"T9551","span":{"begin":1458,"end":1465},"obj":"GO:0007126"},{"id":"T9552","span":{"begin":1537,"end":1542},"obj":"PR:000006549"},{"id":"T9553","span":{"begin":1569,"end":1574},"obj":"PR:000006549"},{"id":"T9554","span":{"begin":1582,"end":1589},"obj":"UBERON:0000025"},{"id":"T9555","span":{"begin":1634,"end":1647},"obj":"CL:0000216"},{"id":"T9556","span":{"begin":1652,"end":1665},"obj":"CL:0000020"},{"id":"T9557","span":{"begin":1688,"end":1709},"obj":"CL:0000656"},{"id":"T9558","span":{"begin":1729,"end":1736},"obj":"UBERON:0000025"},{"id":"T9559","span":{"begin":1745,"end":1765},"obj":"CL:0000228"},{"id":"T9560","span":{"begin":1750,"end":1759},"obj":"GO:0005634"},{"id":"T9561","span":{"begin":1770,"end":1780},"obj":"_FRAGMENT"},{"id":"T9562","span":{"begin":1796,"end":1802},"obj":"CL:0002242"},{"id":"T9563","span":{"begin":1796,"end":1802},"obj":"GO:0005634"},{"id":"T9564","span":{"begin":1823,"end":1838},"obj":"CL:0000445"}],"relations":[{"id":"R2378","pred":"_lexicallyChainedTo","subj":"T9542","obj":"T9541"},{"id":"R2379","pred":"_lexicallyChainedTo","subj":"T9562","obj":"T9561"}],"text":"Breeding of Dmrt7 heterozygotes produced homozygous mutant progeny of both sexes at the expected frequency (63/264; 23%). Male and female homozygous mutants were viable, grew to adulthood normally, and exhibited normal sexual behavior. Female homozygotes were fertile, produced litters of normal size, and had no obvious ovarian abnormalities as judged by histological analysis (unpublished data). In contrast, Dmrt7 homozygous mutant males were completely infertile and had testes about one-third the weight of those of heterozygous or wild-type adult littermates (Figure 2). To determine when defective testis development begins in Dmrt7 mutants, we compared the testes of wild-type and mutant littermates during the first wave of spermatogenesis. Prior to postnatal day 14 (P14), mutant testes appeared histologically normal and the testis weights were similar to those of heterozygous and wild-type littermates, indicating that spermatogonia and early meiotic germ cells form normally (Figure 2B; unpublished data). Thereafter, the testes of the Dmrt7 mutant mice ceased to grow and the weight difference was significant. Microscopic examination of P21 and P42 Dmrt7 mutant testes revealed that germ cells arrest in pachynema, and later stages of germ cells are largely missing (Figure 2C and 2D). Dmrt7 mutant mice are deficient in postmeiotic spermatids and lack epididymal spermatozoa, although a few cells develop to the round spermatid stage. These meiotic defects are in agreement with a recent preliminary analysis of another Dmrt7 mutation [42]. While some Dmrt7 mutant tubules are highly vacuolated and contain primarily Sertoli cells and spermatogonia, others have abundant primary spermatocytes. In addition, some tubules contain multinucleated cells and cells with darkly stained nuclei that are typical of apoptotic cells (Figure 2D)."}

    craft-ca-core-ex-dev

    {"project":"craft-ca-core-ex-dev","denotations":[{"id":"T9595","span":{"begin":0,"end":8},"obj":"GO_EXT:breeding"},{"id":"T9596","span":{"begin":12,"end":17},"obj":"PR_EXT:000006549"},{"id":"T9597","span":{"begin":52,"end":58},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9598","span":{"begin":122,"end":126},"obj":"PATO_UBERON_EXT:male_or_bearer_of_maleness"},{"id":"T9599","span":{"begin":131,"end":137},"obj":"PATO_UBERON_EXT:female_or_bearer_of_femaleness"},{"id":"T9600","span":{"begin":149,"end":156},"obj":"SO_EXT:sequence_altered_entity"},{"id":"T9601","span":{"begin":170,"end":174},"obj":"GO:0040007"},{"id":"T9602","span":{"begin":178,"end":187},"obj":"UBERON:0000113"},{"id":"T9603","span":{"begin":219,"end":234},"obj":"GO:0019098"},{"id":"T9604","span":{"begin":236,"end":242},"obj":"PATO_UBERON_EXT:female_or_bearer_of_femaleness"},{"id":"T9605","span":{"begin":321,"end":328},"obj":"UBERON:0000992"},{"id":"T9606","span":{"begin":411,"end":416},"obj":"PR_EXT:000006549"},{"id":"T9607","span":{"begin":428,"end":434},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9608","span":{"begin":435,"end":440},"obj":"PATO_UBERON_EXT:male_or_bearer_of_maleness"},{"id":"T9609","span":{"begin":475,"end":481},"obj":"UBERON:0000473"},{"id":"T9610","span":{"begin":537,"end":546},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T9611","span":{"begin":547,"end":552},"obj":"UBERON:0007023"},{"id":"T9612","span":{"begin":605,"end":611},"obj":"UBERON:0000473"},{"id":"T9613","span":{"begin":605,"end":623},"obj":"GO:0008584"},{"id":"T9614","span":{"begin":634,"end":639},"obj":"PR_EXT:000006549"},{"id":"T9615","span":{"begin":640,"end":647},"obj":"SO_EXT:sequence_altered_entity"},{"id":"T9616","span":{"begin":665,"end":671},"obj":"UBERON:0000473"},{"id":"T9617","span":{"begin":675,"end":684},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T9618","span":{"begin":689,"end":695},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9619","span":{"begin":733,"end":748},"obj":"GO:0007283"},{"id":"T9620","span":{"begin":763,"end":768},"obj":"GO:0007567"},{"id":"T9621","span":{"begin":783,"end":789},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9622","span":{"begin":790,"end":796},"obj":"UBERON:0000473"},{"id":"T9623","span":{"begin":836,"end":842},"obj":"UBERON:0000473"},{"id":"T9624","span":{"begin":893,"end":902},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T9625","span":{"begin":932,"end":945},"obj":"CL:0000020"},{"id":"T9626","span":{"begin":956,"end":963},"obj":"GO:0007126"},{"id":"T9627","span":{"begin":964,"end":974},"obj":"CL:0000586"},{"id":"T9628","span":{"begin":969,"end":974},"obj":"CL_GO_EXT:cell"},{"id":"T9629","span":{"begin":1036,"end":1042},"obj":"UBERON:0000473"},{"id":"T9630","span":{"begin":1050,"end":1055},"obj":"PR_EXT:000006549"},{"id":"T9631","span":{"begin":1056,"end":1062},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9632","span":{"begin":1063,"end":1067},"obj":"NCBITaxon:10088"},{"id":"T9633","span":{"begin":1078,"end":1082},"obj":"GO:0040007"},{"id":"T9634","span":{"begin":1165,"end":1170},"obj":"PR_EXT:000006549"},{"id":"T9635","span":{"begin":1171,"end":1177},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9636","span":{"begin":1178,"end":1184},"obj":"UBERON:0000473"},{"id":"T9637","span":{"begin":1199,"end":1209},"obj":"CL:0000586"},{"id":"T9638","span":{"begin":1204,"end":1209},"obj":"CL_GO_EXT:cell"},{"id":"T9639","span":{"begin":1220,"end":1229},"obj":"GO:0000239"},{"id":"T9640","span":{"begin":1241,"end":1250},"obj":"_FRAGMENT"},{"id":"T9641","span":{"begin":1256,"end":1261},"obj":"GO:0022403"},{"id":"T9642","span":{"begin":1251,"end":1261},"obj":"CL:0000586"},{"id":"T9643","span":{"begin":1256,"end":1261},"obj":"CL_GO_EXT:cell"},{"id":"T9644","span":{"begin":1302,"end":1307},"obj":"PR_EXT:000006549"},{"id":"T9645","span":{"begin":1308,"end":1314},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9646","span":{"begin":1315,"end":1319},"obj":"NCBITaxon:10088"},{"id":"T9647","span":{"begin":1341,"end":1348},"obj":"GO:0007126"},{"id":"T9648","span":{"begin":1349,"end":1359},"obj":"CL:0000018"},{"id":"T9649","span":{"begin":1369,"end":1379},"obj":"UBERON:0001301"},{"id":"T9650","span":{"begin":1380,"end":1391},"obj":"CL:0000019"},{"id":"T9651","span":{"begin":1408,"end":1413},"obj":"CL_GO_EXT:cell"},{"id":"T9652","span":{"begin":1435,"end":1444},"obj":"CL:0000018"},{"id":"T9653","span":{"begin":1458,"end":1465},"obj":"GO:0007126"},{"id":"T9654","span":{"begin":1537,"end":1542},"obj":"PR_EXT:000006549"},{"id":"T9655","span":{"begin":1543,"end":1551},"obj":"SO_EXT:sequence_alteration_entity_or_process"},{"id":"T9656","span":{"begin":1569,"end":1574},"obj":"PR_EXT:000006549"},{"id":"T9657","span":{"begin":1575,"end":1581},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T9658","span":{"begin":1582,"end":1589},"obj":"UBERON:00000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of Dmrt7 heterozygotes produced homozygous mutant progeny of both sexes at the expected frequency (63/264; 23%). Male and female homozygous mutants were viable, grew to adulthood normally, and exhibited normal sexual behavior. Female homozygotes were fertile, produced litters of normal size, and had no obvious ovarian abnormalities as judged by histological analysis (unpublished data). In contrast, Dmrt7 homozygous mutant males were completely infertile and had testes about one-third the weight of those of heterozygous or wild-type adult littermates (Figure 2). To determine when defective testis development begins in Dmrt7 mutants, we compared the testes of wild-type and mutant littermates during the first wave of spermatogenesis. Prior to postnatal day 14 (P14), mutant testes appeared histologically normal and the testis weights were similar to those of heterozygous and wild-type littermates, indicating that spermatogonia and early meiotic germ cells form normally (Figure 2B; unpublished data). Thereafter, the testes of the Dmrt7 mutant mice ceased to grow and the weight difference was significant. Microscopic examination of P21 and P42 Dmrt7 mutant testes revealed that germ cells arrest in pachynema, and later stages of germ cells are largely missing (Figure 2C and 2D). Dmrt7 mutant mice are deficient in postmeiotic spermatids and lack epididymal spermatozoa, although a few cells develop to the round spermatid stage. These meiotic defects are in agreement with a recent preliminary analysis of another Dmrt7 mutation [42]. While some Dmrt7 mutant tubules are highly vacuolated and contain primarily Sertoli cells and spermatogonia, others have abundant primary spermatocytes. In addition, some tubules contain multinucleated cells and cells with darkly stained nuclei that are typical of apoptotic cells (Figure 2D)."}