Phenotypes associated with this allele

• Allele Symbol: Bin1^tm1Gcp
• Allele Name: targeted mutation 1, George C Prendergast
• Allele ID: MGI:2664484
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bin1^tm1Gcp/Bin1^tm1Gcp	involves: 129S6/SvEvTac * C57BL/6J	MGI:2664487
cn2	Bin1^tm1Gcp/Bin1^tm2Gcp Tg(MMTV-Myc)141-3Led/0 Tg(Wap-cre)11738Mam/0	involves: 129S6/SvEvTac * C57BL/6 * CD-1 * FVB/N * SJL	MGI:3697474
cn3	Bin1^tm1Gcp/Bin1^tm2Gcp Tg(Wap-cre)11738Mam/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL	MGI:3793422

Genotype
MGI:2664487

hm1

• Allelic Composition: Bin1^tm1Gcp/Bin1^tm1Gcp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

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

mortality/aging

neonatal lethality, complete penetrance ( J:83753 )

• most homozygous mutant mice fail to nurse, grow weak, and die within the first 24 hours after birth

cardiovascular system

abnormal myocardial fiber morphology ( J:83753 )

• loosely packed, disorganized cardiac myofibrils; myofibrils of the skeletal muscle are less severely affected

• skeletal muscle cell differentiation and T-tubule formation appear normal

disorganized myocardium ( J:83753 )

• more densely packed myocardiocytes

thick ventricular wall ( J:83753 )

• the heart is markedly increased in thickness, resulting in occlusion of both ventricular chambers

ventricular cardiomyopathy ( J:83753 )

• hypertrophy and disarray of ventricular cardiomyocytes

muscle

abnormal myocardial fiber morphology ( J:83753 )

• loosely packed, disorganized cardiac myofibrils; myofibrils of the skeletal muscle are less severely affected

• skeletal muscle cell differentiation and T-tubule formation appear normal

disorganized myocardium ( J:83753 )

• more densely packed myocardiocytes

ventricular cardiomyopathy ( J:83753 )

• hypertrophy and disarray of ventricular cardiomyocytes

abnormal sarcomere morphology ( J:83753 )

• sarcomeric structures appear disrupted

abnormal A band morphology ( J:83753 )

• no apparent A bands

diffuse Z line ( J:83753 )

• diffuse Z lines

behavior/neurological

abnormal suckling behavior ( J:83753 )

• moribund pups are unable to nurse

cellular

cellular phenotype ( J:83753 )

N • no abnormalities are observed in mouse embryonic fibroblasts with respect to endocytosis, actin cytoskeletal organization, or serum deprival-induced apoptosis

immune system

immune system phenotype ( J:83753 )

N • macrophages from homozygous mutant mice display normal phagocytic uptake

Genotype
MGI:3697474

cn2

• Allelic Composition: Bin1^tm1Gcp/Bin1^tm2Gcp; Tg(MMTV-Myc)141-3Led/0; Tg(Wap-cre)11738Mam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CD-1 * FVB/N * SJL

neoplasm

increased mammary adenocarcinoma incidence ( J:117330 )

increased lymphoma incidence ( J:117330 )

• some mice develop aggressive lymphomas which occasionally appear before mammary carcinomas

cellular

abnormal cell physiology ( J:117330 )

• tumor cells show increased motility in monolayer culture

decreased apoptosis ( J:117330 )

• tumor cells in culture show several fold greater resistance to serum deprivation-induced apoptosis

increased cell proliferation ( J:117330 )

• tumor cells show 3-4 fold higher rates of proliferation under anchorage-dependent conditions

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:117330 )

• tumor cells have higher gelatinase activity

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:117330 )

integument

increased mammary adenocarcinoma incidence ( J:117330 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:117730

Genotype
MGI:3793422

cn3

• Allelic Composition: Bin1^tm1Gcp/Bin1^tm2Gcp; Tg(Wap-cre)11738Mam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

endocrine/exocrine glands

abnormal involution of the mammary gland ( J:117330 )

♀ • ductolobular regression was achieved with somewhat slower kinetics in mutant mice during glandular involution after pregnancy

abnormal mammary gland embryonic development ( J:117330 )

♀ • a delay in the kinetics of ductolobular development was apparent at 18.5 dpc, when mutant mice showed significantly less glandular remodeling

♀ • at 7.5 dpp, this defect had resolved, such that no deficiencies were apparent in nursing and pups showed no signs of malnutrition

increased mammary gland tumor incidence ( J:117330 )

• 8% of elderly animals of >1 year of age exhibited developed poorly differentiated tumors

• DMBA treated animals developed poorly differentiated tumors, characterized by low tubule formation, high mitotic indices, and high degrees of nuclear pleomorphism and relative increase in lymphocyte infiltration compared with mice carrying one wild-type allele of Bin1

increased granulosa cell tumor incidence ( J:117330 )

♀ • ovarian granulosa cell tumors are noted

♀ • increased incidence of DMBA-induced ovarian granulosa cell tumors in mutant mice (43%) relative to mice carrying one wild-type copy of Bim1 (13%), all of whom also had mammary tumors

neoplasm

increased mammary gland tumor incidence ( J:117330 )

• 8% of elderly animals of >1 year of age exhibited developed poorly differentiated tumors

• DMBA treated animals developed poorly differentiated tumors, characterized by low tubule formation, high mitotic indices, and high degrees of nuclear pleomorphism and relative increase in lymphocyte infiltration compared with mice carrying one wild-type allele of Bin1

increased granulosa cell tumor incidence ( J:117330 )

♀ • ovarian granulosa cell tumors are noted

♀ • increased incidence of DMBA-induced ovarian granulosa cell tumors in mutant mice (43%) relative to mice carrying one wild-type copy of Bim1 (13%), all of whom also had mammary tumors

increased incidence of tumors by chemical induction ( J:117330 )

• DMBA treated animals developed poorly differentiated tumors, characterized by low tubule formation, high mitotic indices, and high degrees of nuclear pleomorphism and relative increase in lymphocyte infiltration compared with mice carrying one wild-type allele of Bin1

• increased incidence of DMBA-induced ovarian granulosa cell tumors in mutant mice (43%) relative to mice carrying one wild-type copy of Bim1 (13%), all of whom also had mammary tumors

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:117330 )

• DMBA treated animals developed poorly differentiated tumors, characterized by low tubule formation, high mitotic indices, and high degrees of nuclear pleomorphism and relative increase in lymphocyte infiltration compared with mice carrying one wild-type allele of Bin1

• increased incidence of DMBA-induced ovarian granulosa cell tumors in mutant mice (43%) relative to mice carrying one wild-type copy of Bim1 (13%), all of whom also had mammary tumors

immune system

endometrium inflammation ( J:117330 )

• elevation in uterine endometritis

integument

abnormal involution of the mammary gland ( J:117330 )

♀ • ductolobular regression was achieved with somewhat slower kinetics in mutant mice during glandular involution after pregnancy

abnormal mammary gland embryonic development ( J:117330 )

♀ • a delay in the kinetics of ductolobular development was apparent at 18.5 dpc, when mutant mice showed significantly less glandular remodeling

♀ • at 7.5 dpp, this defect had resolved, such that no deficiencies were apparent in nursing and pups showed no signs of malnutrition

increased mammary gland tumor incidence ( J:117330 )

• 8% of elderly animals of >1 year of age exhibited developed poorly differentiated tumors

• DMBA treated animals developed poorly differentiated tumors, characterized by low tubule formation, high mitotic indices, and high degrees of nuclear pleomorphism and relative increase in lymphocyte infiltration compared with mice carrying one wild-type allele of Bin1

reproductive system

increased granulosa cell tumor incidence ( J:117330 )

♀ • ovarian granulosa cell tumors are noted

♀ • increased incidence of DMBA-induced ovarian granulosa cell tumors in mutant mice (43%) relative to mice carrying one wild-type copy of Bim1 (13%), all of whom also had mammary tumors

endometrium inflammation ( J:117330 )

• elevation in uterine endometritis