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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Men1tm1.2Zqw
targeted mutation 1, Zhao-Qi Wang
MGI:2675250
Summary 2 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Men1tm1.2Zqw/Men1tm1.2Zqw
Pgrtm2(cre)Lyd/Pgr+
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 MGI:7434127
cn2
Men1tm1.2Zqw/Men1tm1.2Zqw
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * CBA/J MGI:2675251


Genotype
MGI:7434127
cn1
Allelic
Composition
Men1tm1.2Zqw/Men1tm1.2Zqw
Pgrtm2(cre)Lyd/Pgr+
Genetic
Background
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1tm1.2Zqw mutation (1 available); any Men1 mutation (40 available)
Pgrtm2(cre)Lyd mutation (0 available); any Pgr mutation (75 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
• although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy
• terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy
• immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy
• FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy
• more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy
• decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization
• after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy
• immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy
• average weight of implantation sites is significantly reduced on days 8 and 9 of pregnancy
• however, blastocyst attachment and implantation appear normal during early pregnancy
• disrupted progression of decidualization leads to miscarriage at mid-gestation, with severe embryo absorption between days 9 and 12 of pregnancy
• when mated with wild type fertile males, only 25% plug-positive 2-month-old females give birth to offspring vs 83% in control females, indicating severe female subfertility
• when mated with wild type fertile males, females produce a significantly smaller litter size than control females

embryo
• embryo development is defective at the post-implantation stage, with severe embryo absorption observed between days 9 and 12 of pregnancy
• embryo growth is retarded in implantation sites on day 8 of pregnancy
• eccentric expression pattern of trophoblast giant cell marker PL1 indicates shallow trophoblast invasion on day 8 of pregnancy
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
• expression of COX2 in the presumptive site of placentation is disordered on day 8 of pregnancy; placentation is obviously abnormal starting on day 9
• although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy
• terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy
• immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy
• FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy
• more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy
• decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization
• after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy

cellular
• reduction of Bmp2 expression caused by aberrant activation of the ERK1/2 signaling pathway disrupts development of the SDZ due to disorganized genomic H3K4me3 modification

endocrine/exocrine glands
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
• immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy

growth/size/body
• embryo growth is retarded in implantation sites on day 8 of pregnancy

hematopoietic system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy

immune system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy




Genotype
MGI:2675251
cn2
Allelic
Composition
Men1tm1.2Zqw/Men1tm1.2Zqw
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1tm1.2Zqw mutation (1 available); any Men1 mutation (40 available)
Tg(Ins2-cre)23Herr mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 41.5% of mice developed insulinomas by 6 months of age and by 10 months, 100% of mutants have advanced insulinomas (carcinomas)

endocrine/exocrine glands
• hyperplastic islets as early as 2 months of age, which progresses with aging
• 41.5% of mice developed insulinomas by 6 months of age and by 10 months, 100% of mutants have advanced insulinomas (carcinomas)

homeostasis/metabolism
• glucose levels decreased after 8 months of agae, as tumorigenesis progressed
• insulin levels increased starting at 4 months of age and continued to increase with age

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
multiple endocrine neoplasia type 1 DOID:10017 OMIM:131100
J:85133





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last database update
12/10/2024
MGI 6.24
The Jackson Laboratory