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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Huwe1tm1Alas
targeted mutation 1, Anna Lasorella
MGI:4439480
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Huwe1tm1Alas/Y
Tg(Prm-cre)58Og/0
involves: 129S4/SvJae * 129S7/SvEvBrd MGI:7286185
cn2
Huwe1tm1Alas/Y
Tg(Nes-cre)1Kag/0
involves: 129S7/SvEvBrd MGI:4821353
cn3
Huwe1tm1Alas/Y
Tg(Spo11-cre)1Rsw/0
involves: 129S7/SvEvBrd MGI:7286184
cn4
Huwe1tm1Alas/Y
Tg(Stra8-icre)1Reb/0
involves: 129S7/SvEvBrd * C57BL/6 * FVB/NJ MGI:7286183


Genotype
MGI:7286185
cn1
Allelic
Composition
Huwe1tm1Alas/Y
Tg(Prm-cre)58Og/0
Genetic
Background
involves: 129S4/SvJae * 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Alas mutation (0 available); any Huwe1 mutation (63 available)
Tg(Prm-cre)58Og mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• male mice are fertile and show normal spermatogenesis with no significant differences in sperm number, sperm motility or testis weights relative to control males




Genotype
MGI:4821353
cn2
Allelic
Composition
Huwe1tm1Alas/Y
Tg(Nes-cre)1Kag/0
Genetic
Background
involves: 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Alas mutation (0 available); any Huwe1 mutation (63 available)
Tg(Nes-cre)1Kag mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

nervous system
• at E13.5, E15.5, E18.5, fewer progenitors exit the cell cycle compared with wild-type mice
• at E18.5, proliferation of neuronal precursors is increased compared to in wild-type mice
• at E18.5, the length of the cycle is lengthened compared to in wild-type cells
• brains contain ectopic cellular clusters in differentiated striatal regions unlike in wild-type mice
• however, no abnormalities are observed at E15.5
• the cortex exhibits an increase in cellular density and decrease in intervening neuropil compared to in wild-type mice
• laminar organization is altered with no clearly identifiable superficial neuron layers compared to in wild-type mice
• very small
• in the germinal layers

cellular
• at E13.5, E15.5, E18.5, fewer progenitors exit the cell cycle compared with wild-type mice
• at E18.5, proliferation of neuronal precursors is increased compared to in wild-type mice
• at E18.5, the length of the cycle is lengthened compared to in wild-type cells




Genotype
MGI:7286184
cn3
Allelic
Composition
Huwe1tm1Alas/Y
Tg(Spo11-cre)1Rsw/0
Genetic
Background
involves: 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Alas mutation (0 available); any Huwe1 mutation (63 available)
Tg(Spo11-cre)1Rsw mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• male mice are fertile and show no apparent defects in spermatogenesis, epididymal sperm number, sperm motility or meiotic progression relative to control males
• chromosome spreads prepared from 28dpp testes show a significantly higher % of spermatocytes that retain gammaH2AX on the autosomes in pachytene and diplotene spermatocytes (where normally gammaH2AX is found only on the XY body)
• however, no significant increase in apoptosis is observed, as determined by a TUNEL assay

cellular
• chromosome spreads prepared from 28dpp testes show a significantly higher % of spermatocytes that retain gammaH2AX on the autosomes in pachytene and diplotene spermatocytes (where normally gammaH2AX is found only on the XY body)
• however, no significant increase in apoptosis is observed, as determined by a TUNEL assay




Genotype
MGI:7286183
cn4
Allelic
Composition
Huwe1tm1Alas/Y
Tg(Stra8-icre)1Reb/0
Genetic
Background
involves: 129S7/SvEvBrd * C57BL/6 * FVB/NJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Alas mutation (0 available); any Huwe1 mutation (63 available)
Tg(Stra8-icre)1Reb mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at 48 days post retinoic acid injection (48dpRA), synchronized adult testes contain fewer Stra8+ pre-leptotene spermatocytes (located away from the basement membrane of the tubules), indicating a defect in spermatogonial differentiation
• at 8 days post retinoic acid injection (8dpRA), synchronized testes show clear loss of pre-leptotene/leptotene spermatocytes (germ cells located away from the basement membrane) in the tubules
• at 8dpRA, the average number of Stra8+ pre-leptotene spermatocytes is significantly reduced in synchronized testes, whereas the number of Stra8+ spermatogonia (located adjacent to the basement membrane) is normal
• staining with SYCP3 (a marker used to identify different types of spermatocytes in meiotic prophase I) confirmed the presence of fewer leptotene spermatocytes at 8dpRA
• at 10 days post-partum (dpp), unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci
• at 48dpRA, spermatogonia differentiation is disrupted in synchronized adult testes, leading to formation of fewer pre-leptotene spermatocytes
• at 48dpRA, expression of markers for differentiating spermatogonia (Stra8, Dazl, Sohlh2) is markedly reduced in synchronized adult testes
• at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci
• significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids are observed in the tubules at 4 months of age
• average cauda epididymal sperm number is only 3% of that in control males
• at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3
• at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes incorporating BrdU in synchronized testes is ~50% lower than in control testes
• however, no difference is noted in the proportion of proliferating Stra8+ A1 spermatogonia at 8dpRA
• at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci, along with recruitment of pCHK2 to these gammaH2AX foci, indicating activation of the DNA damage response pathway
• at 8dpRA, double staining for Tra98 (a germ cell marker) and cleaved caspase 3 showed a significant increase in male germ cell apoptosis in synchronized testes relative to control testes (~68% versus 46%, respectively)
• no significant colocalization of p53 with gammaH2AX foci is observed, suggesting p53-independent apoptosis
• adult males have significantly smaller testes than control males
• average weight of adult testes is only 30% of control males
• at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes is reduced by ~50% while expression of early meiotic markers (Spo11, Smc1b, Sycp1, Sycp3) is significantly decreased in synchronized testes, indicating impaired entry into meiosis
• at 4 months of age, males show significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids in the seminiferous tubules, indicating a developmental arrest early in spermatogenesis
• few sperm are present in the caput epididymis
• males fail to sire any litters during a 4-week fertility assay
• however, the frequency of vaginal plugging is normal

cellular
• at 48 days post retinoic acid injection (48dpRA), synchronized adult testes contain fewer Stra8+ pre-leptotene spermatocytes (located away from the basement membrane of the tubules), indicating a defect in spermatogonial differentiation
• at 8 days post retinoic acid injection (8dpRA), synchronized testes show clear loss of pre-leptotene/leptotene spermatocytes (germ cells located away from the basement membrane) in the tubules
• at 8dpRA, the average number of Stra8+ pre-leptotene spermatocytes is significantly reduced in synchronized testes, whereas the number of Stra8+ spermatogonia (located adjacent to the basement membrane) is normal
• staining with SYCP3 (a marker used to identify different types of spermatocytes in meiotic prophase I) confirmed the presence of fewer leptotene spermatocytes at 8dpRA
• at 10 days post-partum (dpp), unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci
• at 48dpRA, spermatogonia differentiation is disrupted in synchronized adult testes, leading to formation of fewer pre-leptotene spermatocytes
• at 48dpRA, expression of markers for differentiating spermatogonia (Stra8, Dazl, Sohlh2) is markedly reduced in synchronized adult testes
• at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci
• significant loss of differentiating spermatogonia, spermatocytes and extensive loss of spermatids are observed in the tubules at 4 months of age
• average cauda epididymal sperm number is only 3% of that in control males
• at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3
• at 8dpRA, the proportion of proliferating Stra8+ pre-leptotene spermatocytes incorporating BrdU in synchronized testes is ~50% lower than in control testes
• however, no difference is noted in the proportion of proliferating Stra8+ A1 spermatogonia at 8dpRA
• at 10 dpp, unsynchronized testes show an increased proportion of Stra8+ differentiating spermatogonia/pre-leptotene spermatocytes with intense gammaH2AX foci, along with recruitment of pCHK2 to these gammaH2AX foci, indicating activation of the DNA damage response pathway
• at 8dpRA, double staining for Tra98 (a germ cell marker) and cleaved caspase 3 showed a significant increase in male germ cell apoptosis in synchronized testes relative to control testes (~68% versus 46%, respectively)
• no significant colocalization of p53 with gammaH2AX foci is observed, suggesting p53-independent apoptosis

endocrine/exocrine glands
• at 8dpRA, synchronized testes show a significantly higher % of TUNEL+ tubules than control testes; similar results are obtained by staining the same sections with cleaved, activated caspase 3
• adult males have significantly smaller testes than control males
• average weight of adult testes is only 30% of control males





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last database update
04/23/2024
MGI 6.23
The Jackson Laboratory