Phenotypes associated with this allele

• Allele Symbol: Brca1^tm1Bhk
• Allele Name: targeted mutation 1, Beverly H Koller
• Allele ID: MGI:1857931
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Brca1^tm1Bhk/Brca1^tm1Bhk	involves: 129P2/OlaHsd * BALB/c * C57BL/6	MGI:3814403
hm2	Brca1^tm1Bhk/Brca1^tm1Bhk	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2174676
ht3	Brca1^tm1Bhk/Brca1^+	C.129P2-Brca1^tm1Bhk	MGI:5517368
ht4	Brca1^tm1Bhk/Brca1^+	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:2174677
cx5	Brca1^tm1Bhk/Brca1^tm1Bhk Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk	MGI:5517367
cx6	Brca1^tm1Bhk/Brca1^+ Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi	C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk	MGI:5517370

Genotype
MGI:3814403

hm1

• Allelic Composition: Brca1^tm1Bhk/Brca1^tm1Bhk
• Genetic Background: involves: 129P2/OlaHsd * BALB/c * C57BL/6

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

mortality/aging

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

• lethality occurs around E10.5; survival is not altered with incorporation of BALB/c genetic background

nervous system

open neural tube ( J:74077 )

• embryos characteristically exhibit an open cranial neural tube at E8-E8.5

embryo

open neural tube ( J:74077 )

• embryos characteristically exhibit an open cranial neural tube at E8-E8.5

Genotype
MGI:2174676

hm2

• Allelic Composition: Brca1^tm1Bhk/Brca1^tm1Bhk
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:31571 )

• embryos die around E9.5 - E10.5

embryo

decreased embryo size ( J:31571 )

• embryos appear underdeveloped by E8.5 and are clearly smaller at E9.5

abnormal embryonic neuroepithelial layer differentiation ( J:31571 )

• abnormal contours in the neuroepithelium are seen

• excessive cell death is noted in selected cell populations, especially in the hindbrain

open neural tube ( J:31571 )

• fail to close the neural tube completely

spina bifida ( J:31571 )

• variable degrees of severity are observed

nervous system

abnormal embryonic neuroepithelial layer differentiation ( J:31571 )

• abnormal contours in the neuroepithelium are seen

• excessive cell death is noted in selected cell populations, especially in the hindbrain

open neural tube ( J:31571 )

• fail to close the neural tube completely

spina bifida ( J:31571 )

• variable degrees of severity are observed

exencephaly ( J:31571 )

• variable degrees of severity are observed

growth/size/body

decreased embryo size ( J:31571 )

• embryos appear underdeveloped by E8.5 and are clearly smaller at E9.5

Genotype
MGI:5517368

ht3

• Allelic Composition: Brca1^tm1Bhk/Brca1⁺
• Genetic Background: C.129P2-Brca1^tm1Bhk

cellular

decreased mammary gland epithelial cell proliferation ( J:198018 )

• cellular proliferation is inhibited in young and old mammary epithelial cells

early cellular replicative senescence ( J:198018 )

endocrine/exocrine glands

decreased mammary gland epithelial cell proliferation ( J:198018 )

• cellular proliferation is inhibited in young and old mammary epithelial cells

increased mammary gland tumor incidence ( J:198018 )

• less than 10% of mutants develop mammary tumors

growth/size/body

decreased body weight ( J:198018 )

• decrease in body weight from 12 to 24 weeks of age

integument

decreased mammary gland epithelial cell proliferation ( J:198018 )

• cellular proliferation is inhibited in young and old mammary epithelial cells

increased mammary gland tumor incidence ( J:198018 )

• less than 10% of mutants develop mammary tumors

neoplasm

increased mammary gland tumor incidence ( J:198018 )

• less than 10% of mutants develop mammary tumors

Genotype
MGI:2174677

ht4

• Allelic Composition: Brca1^tm1Bhk/Brca1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

normal phenotype

no abnormal phenotype detected ( J:31571 )

• no aberrant phenotype is seen up to 5 months of age

Genotype
MGI:5517367

cx5

• Allelic Composition: Brca1^tm1Bhk/Brca1^tm1Bhk; Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:198018 )

• no viable embryos are identified beyond E14.5

Genotype
MGI:5517370

cx6

• Allelic Composition: Brca1^tm1Bhk/Brca1⁺; Cdkn2c^tm1Yxi/Cdkn2c^tm1Yxi
• Genetic Background: C.129-Cdkn2c^tm1Yxi Brca1^tm1Bhk

endocrine/exocrine glands

abnormal mammary gland morphology ( J:198018 )

♀ • mammary glands of virgin females show a decrease in the expansion of luminal progenitors seen in single Cdkn2c homozygotes to normal levels but show an increase in the expansion of basal/myoepithelial cells

increased mammary gland tumor incidence ( J:198018 )

♀ • 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age

♀ • mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis

♀ • mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

integument

abnormal mammary gland morphology ( J:198018 )

♀ • mammary glands of virgin females show a decrease in the expansion of luminal progenitors seen in single Cdkn2c homozygotes to normal levels but show an increase in the expansion of basal/myoepithelial cells

increased mammary gland tumor incidence ( J:198018 )

♀ • 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age

♀ • mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis

♀ • mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

neoplasm

increased mammary gland tumor incidence ( J:198018 )

♀ • 38% of mutants develop breast cancer before 1 year of age and 87% by 22 months of age

♀ • mammary tumors show high degree of heterogeneity, increased population of CK5+ cells, loss of wild-type allele of Brca1 in CK5+ tumor cells, ERalpha negativity and invasiveness and metastasis

♀ • mammary tumors are transformed from a luminal subtype that is seen in single Cdkn2c homozygotes into a basal-like subtype

increased mammary adenocarcinoma incidence ( J:198018 )

♀ • poorly differentiated carcinoma with squamous metaplasia

increased metastatic potential ( J:198018 )

• 4 of 13 (31%) mammary tumors metastasize to the lung and blood vessels after 1 year of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:198018