Mouse Genome Informatics
hm1
    Brca2tm1Mbn/Brca2tm1Mbn
C.129P2-Brca2tm1Mbn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is extended to about E10.5 on a BALB/c genetic background, compared to E8.5 on a 129/B6 background

embryogenesis
• at E10.5, single surviving embryo displayed open cranial neural tube as in normal E8.5 embryos, but mutant embryo had completed turning and second branchial arch and heart were prominent
• at E8.5, embryos are smaller and show developmental delay compared to littermates; embryos resemble E6-E7-aged embryos at E8.5

growth/size/body
• at E8.5, embryos are smaller and show developmental delay compared to littermates; embryos resemble E6-E7-aged embryos at E8.5

nervous system
• at E10.5, single surviving embryo displayed open cranial neural tube as in normal E8.5 embryos, but mutant embryo had completed turning and second branchial arch and heart were prominent


Mouse Genome Informatics
hm2
    Brca2tm1Mbn/Brca2tm1Mbn
involves: 129P2/OlaHsd * 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryos die before E8.5 and most are resorbed by this time


Mouse Genome Informatics
ht3
    Brca2tm1Mbn/Brca2+
B6.Cg-Brca2tm1Mbn ApcMin
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
N
• body weight of mice at time of sacrifice does not differ significantly from Apc-heterozygous or wild-type animals; weight gain over experiment duration is similar to that of wild-type animals (J:67445)

reproductive system
N
• only observed in 1/10 ENU-treated males, similar to wild-type males (1/9) (J:67445)

tumorigenesis
• females develop mammary tumors at an incidence rate of 23% with a mean tumor multiplicity rate of 0.3 +/- 0.5 (J:67445)
• no males develop mammary tumors (J:67445)

endocrine/exocrine glands
• females exhibit some adrenal hyperplasia, while none is observed in males (J:67445)

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:67445


Mouse Genome Informatics
ht4
    Brca2tm1Mbn/Brca2+
involves: 129P2/OlaHsd * 129S/SvEv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• virgin females display no increased incidence of spontaneous tumors relative to wild-type littermates up to 2 years of age


Mouse Genome Informatics
cx5
    ApcMin/Apc+
Brca2tm1Mbn/Brca2+

B6.Cg-Brca2tm1Mbn ApcMin
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
N
• body weight of mice at time of sacrifice does not differ significantly from Apc-heterozygous, Brca2-heterozygous, or wild-type animals (J:67445)

reproductive system
N
• only observed in 1/8 ENU-treated males, similar to wild-type males (1/9) (J:67445)
• absent in 22% of ENU-treated females (J:67445)
• remaining follicles are degenerating in ENU-treated females (J:67445)
• arrested follicular development is 6-fold more prevalent compared to ENU-treated Brca2-deficient mice (J:67445)
• complete loss of follicles (ovarian atrophy) is observed in about 25% of ENU-treated mutants, whereas almost no incidence is observed in ENU-treated wild-type or Brca2-mutant females (J:67445)
• observed in ENU-treated females displaying ovarian failure (atrophy); endometrium and myometrium appear immature (J:67445)
• reduced in thickness and lined with vacuolated cells indicative of anestrus in ENU-treated females (J:67445)

tumorigenesis
• multiple intestinal tumors are observed in ENU-treated mice
• by 65 days after ENU treatment, 100% of females develop mammary tumors with a multiplicity of 7.2 +/- 2.7, whereas only 7% of wild-type females develop tumors
• males develop tumors at a very low incidence and with a tumor multiplicity of 0.2 +/- 0.3, whereas no wild-type or Brca2-heterozygous males developed mammary tumors
• tumors in male and female mice are adenoacanthomas, characterized by undifferentiated acini and tubules with centrally confined squamous cells and keratin; most tumors contain proportions of adenomatous and squamous cell types
• tumors with predominantly squamous differentiation, moderate to marked inflammation in and around tumors is observed, with areas of fibrosis; in some cases, squamous component becomes cystic and is filled with keratinous debris
• invasion or metastases into the mammary lymph nodes was not observed during time course of study

endocrine/exocrine glands
• in ENU treated mice, male mammary ducts are elongated and in most males have extended to the lymph node of the fourth mammary gland, whereas wild-type and Brca2-heterozygous males are born with a small mammary gland rudiment, which grows no further, and no nipple (J:67445)
• no differences are observed in branching of female mammary glands among genotypes or wild-type females (J:67445)
(J:67445)
• absent in 22% of ENU-treated females (J:67445)
• remaining follicles are degenerating in ENU-treated females (J:67445)
• arrested follicular development is 6-fold more prevalent compared to ENU-treated Brca2-deficient mice (J:67445)
• complete loss of follicles (ovarian atrophy) is observed in about 25% of ENU-treated mutants, whereas almost no incidence is observed in ENU-treated wild-type or Brca2-mutant females (J:67445)

homeostasis/metabolism

integument
• in ENU treated mice, male mammary ducts are elongated and in most males have extended to the lymph node of the fourth mammary gland, whereas wild-type and Brca2-heterozygous males are born with a small mammary gland rudiment, which grows no further, and no nipple (J:67445)
• no differences are observed in branching of female mammary glands among genotypes or wild-type females (J:67445)
(J:67445)

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:67445