Phenotypes associated with this allele

• Allele Symbol: Brca2^tm1Mbn
• Allele Name: targeted mutation 1, L Michelle Bennett
• Allele ID: MGI:2387337
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Brca2^tm1Mbn/Brca2^tm1Mbn	C.129P2-Brca2^tm1Mbn	MGI:3814401
hm2	Brca2^tm1Mbn/Brca2^tm1Mbn	involves: 129P2/OlaHsd * 129S/SvEv	MGI:3814400
ht3	Brca2^tm1Mbn/Brca2^+	B6.Cg-Brca2^tm1Mbn Apc^Min	MGI:3814365
ht4	Brca2^tm1Mbn/Brca2^+	involves: 129P2/OlaHsd * 129S/SvEv	MGI:3814399
cx5	Apc^Min/Apc^+ Brca2^tm1Mbn/Brca2^+	B6.Cg-Brca2^tm1Mbn Apc^Min	MGI:3814367

Genotype
MGI:3814401

hm1

• Allelic Composition: Brca2^tm1Mbn/Brca2^tm1Mbn
• Genetic Background: C.129P2-Brca2^tm1Mbn

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:74077 )

• survival is extended to about E10.5 on a BALB/c genetic background, compared to E8.5 on a 129/B6 background

embryo

embryonic growth retardation ( J:74077 )

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

open neural tube ( J:74077 )

• 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

growth/size/body

embryonic growth retardation ( J:74077 )

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

nervous system

open neural tube ( J:74077 )

• 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

Genotype
MGI:3814400

hm2

• Allelic Composition: Brca2^tm1Mbn/Brca2^tm1Mbn
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv

mortality/aging

embryonic lethality between somite formation and embryo turning, complete penetrance ( J:74077 )

• embryos die before E8.5 and most are resorbed by this time

Genotype
MGI:3814365

ht3

• Allelic Composition: Brca2^tm1Mbn/Brca2⁺
• Genetic Background: B6.Cg-Brca2^tm1Mbn Apc^Min

growth/size/body

growth/size/body region phenotype ( J:67445 )

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

integument

increased mammary gland tumor incidence ( J:67445 )

♀ • females develop mammary tumors at an incidence rate of 23% with a mean tumor multiplicity rate of 0.3 +/- 0.5

♀ • no males develop mammary tumors

reproductive system

reproductive system phenotype ( J:67445 )

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

neoplasm

increased mammary gland tumor incidence ( J:67445 )

♀ • females develop mammary tumors at an incidence rate of 23% with a mean tumor multiplicity rate of 0.3 +/- 0.5

♀ • no males develop mammary tumors

endocrine/exocrine glands

adrenal gland hyperplasia ( J:67445 )

♀ • females exhibit some adrenal hyperplasia, while none is observed in males

increased mammary gland tumor incidence ( J:67445 )

♀ • females develop mammary tumors at an incidence rate of 23% with a mean tumor multiplicity rate of 0.3 +/- 0.5

♀ • no males develop mammary tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:67445

Genotype
MGI:3814399

ht4

• Allelic Composition: Brca2^tm1Mbn/Brca2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:74077 )

• virgin females display no increased incidence of spontaneous tumors relative to wild-type littermates up to 2 years of age

Genotype
MGI:3814367

cx5

• Allelic Composition: Apc^Min/Apc⁺; Brca2^tm1Mbn/Brca2⁺
• Genetic Background: B6.Cg-Brca2^tm1Mbn Apc^Min

growth/size/body

growth/size/body region phenotype ( J:67445 )

N • body weight of mice at time of sacrifice does not differ significantly from Apc-heterozygous, Brca2-heterozygous, or wild-type animals

reproductive system

reproductive system phenotype ( J:67445 )

N • only observed in 1/8 ENU-treated males, similar to wild-type males (1/9)

absent corpus luteum ( J:67445 )

♀ • absent in 22% of ENU-treated females

abnormal ovarian follicle morphology ( J:67445 )

♀ • remaining follicles are degenerating in ENU-treated females

abnormal ovarian folliculogenesis ( J:67445 )

♀ • arrested follicular development is 6-fold more prevalent compared to ENU-treated Brca2-deficient mice

absent mature ovarian follicles ( J:67445 )

♀

ovary atrophy ( 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

uterus atrophy ( J:67445 )

♀ • observed in ENU-treated females displaying ovarian failure (atrophy); endometrium and myometrium appear immature

abnormal vagina epithelium morphology ( J:67445 )

♀ • reduced in thickness and lined with vacuolated cells indicative of anestrus in ENU-treated females

neoplasm

increased mammary gland tumor incidence ( J:67445 )

• 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

increased incidence of induced tumors ( J:67445 )

• multiple intestinal tumors are observed in ENU-treated mice

increased incidence of tumors by chemical induction ( J:67445 )

endocrine/exocrine glands

abnormal adrenal gland morphology ( J:67445 )

abnormal mammary gland development ( J:67445 )

♂ • 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

♂ • no differences are observed in branching of female mammary glands among genotypes or wild-type females

absent nipple ( J:67445 )

♀

increased mammary gland tumor incidence ( J:67445 )

• 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

absent corpus luteum ( J:67445 )

♀ • absent in 22% of ENU-treated females

abnormal ovarian follicle morphology ( J:67445 )

♀ • remaining follicles are degenerating in ENU-treated females

abnormal ovarian folliculogenesis ( J:67445 )

♀ • arrested follicular development is 6-fold more prevalent compared to ENU-treated Brca2-deficient mice

absent mature ovarian follicles ( J:67445 )

♀

ovary atrophy ( 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

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:67445 )

integument

abnormal mammary gland development ( J:67445 )

♂ • 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

♂ • no differences are observed in branching of female mammary glands among genotypes or wild-type females

absent nipple ( J:67445 )

♀

increased mammary gland tumor incidence ( J:67445 )

• 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:67445