Mouse Genome Informatics
cn1
    Tg(CAG-Has2)99Nita/0
Tg(MMTV-cre)4Mam/0
Tg(MMTVneu)202Mul/0

FVB.Cg-Tg(CAG-Has2)99Nita Tg(MMTV-cre)4Mam Tg(MMTVneu)202Mul
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis

hematopoietic system
• after macrophage depletion with encapsulated clodronate blood vessels in tumors were mostly small and fragmented
• density of invading macrophage is 7-fold greater in the stroma of tumors compared with Neo in-control

immune system
• after macrophage depletion with encapsulated clodronate blood vessels in tumors were mostly small and fragmented
• density of invading macrophage is 7-fold greater in the stroma of tumors compared with Neo in-control
• mammary gland tumors express more podoplanin+ lymphatic endothelial cells than in Tg(MMTVneu)202Mul Tg(CAG-Has2)99Nita mice
• intratumoral lyphatics are 16-fold greater than in Tg(MMTVneu)202Mul Tg(CAG-Has2)99Nita mice while peritumoral lymphatic vessels are only 1.5-fold greater
• tumor lymphatic vessels are associated with high hyaluronan stroma

cellular
• after macrophage depletion with encapsulated clodronate blood vessels in tumors were mostly small and fragmented

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:164205


Mouse Genome Informatics
cn2
    Cdkn1btm1Mlf/Cdkn1b+
Crebbptm1Jvd/Crebbptm1Jvd
Tg(MMTV-cre)4Mam/0

involves: 129 * C57BL/6 * CBA * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• considerably accelerated tumor development


Mouse Genome Informatics
cn3
    n-Ts2tm1Dhat/n-Ts2tm1Dhat
Tg(MMTV-cre)4Mam/0

involves: 129 * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• normal mammary development and normal lactation (J:82321)


Mouse Genome Informatics
cn4
    Crebbptm1Jvd/Crebbptm1Jvd
Tg(MMTV-cre)4Mam/0

involves: 129 * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• increased percentage of CD8-SP thymocytes
• decreased percentage of double positive cells

tumorigenesis
• 59% of mice develop fatal T-cell lymphomas between 3 and 9 months of age
• remaining animals continue healthy past 10 months of age

hematopoietic system
• increased percentage of CD8-SP thymocytes
• decreased percentage of double positive cells


Mouse Genome Informatics
cn5
    Mysm1tm1a(KOMP)Wtsi/Mysm1tm1a(KOMP)Wtsi
Tg(MMTV-cre)4Mam/0

involves: 129 * C57BL/6N * FVB

cell line(s): EPD0019_1_A04
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• absolute numbers of all hematopoietic cell lineages are reduced to varying degrees
• however the frequencies of CD3+ T and CD4+ T lymphocytes, Gr1+CD11b+ myeloid cells, Ter119+ erythrocytes, and CD41+Ter119- megakaryocytes are largely normal or elevated in various tissues
• dramatic decrease in the percentage of B220+ CD19+ B cells in the bone marrow, spleen, peripheral blood, and lymph nodes compared to littermate controls
• marked reduction the number of peripheral B cells that express surface IgM and IgD mice have only 0.25% of control B cell numbers
• reduction in the number and frequency of pre-pro-B cells in the bone marrow
• dramatic reduction in pre-B cell frequency and absolute numbers in bone marrow
• dramatic reduction in pro-B cell frequency and absolute numbers in bone marrow
• in an in vitro pre-B cell colony forming assay no B cell colonies are formed from bone marrow cells
• the frequency of DN1 cells is increased and the frequency of DN2 cells is reduced; however, the frequencies of DP and DN cells are roughly equal
• most cells in the CLP population are Ly6D- all-lymphoid progenitors with only a few Ly6D+ B cell biased lymphoid progenitors detected

growth/size

limbs/digits/tail
• truncated tail

immune system
• dramatic decrease in the percentage of B220+ CD19+ B cells in the bone marrow, spleen, peripheral blood, and lymph nodes compared to littermate controls
• marked reduction the number of peripheral B cells that express surface IgM and IgD mice have only 0.25% of control B cell numbers
• reduction in the number and frequency of pre-pro-B cells in the bone marrow
• dramatic reduction in pre-B cell frequency and absolute numbers in bone marrow
• dramatic reduction in pro-B cell frequency and absolute numbers in bone marrow
• in an in vitro pre-B cell colony forming assay no B cell colonies are formed from bone marrow cells
• the frequency of DN1 cells is increased and the frequency of DN2 cells is reduced; however, the frequencies of DP and DN cells are roughly equal
• most cells in the CLP population are Ly6D- all-lymphoid progenitors with only a few Ly6D+ B cell biased lymphoid progenitors detected


Mouse Genome Informatics
cn6
    St14tm2Bug/St14tm3Bug
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
N
• mice exhibit normal salivary gland morphology (J:153070)
• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice

endocrine/exocrine glands
• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice

homeostasis/metabolism
• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice


Mouse Genome Informatics
cn7
    Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan/Gt(ROSA)26Sor+
Trp53tm1Brn/Trp53tm1Brn
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die early with lymphoma/thymoma

tumorigenesis
• some mice have small mammary tumors


Mouse Genome Informatics
cn8
    Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan/Gt(ROSA)26Sor+
Trp53tm1Brn/Trp53+
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is reduced compared to mutant mice wild-type for Trp53

tumorigenesis
• at a lower rate than in mutant mice homozygous for Trp53tm1Brn
• 80% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or adenosquamous carcinoma
• radial scar and poorly differentiated adenocarcinomas are also observed, although at a lower frequency than in mutant mice not carrying Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:170898


Mouse Genome Informatics
cn9
    Map2k7tm1.1Twad/Map2k7tm1.2Twad
Tg(MMTV-cre)4Mam/0
Tg(MMTV-Erbb2)1Pv/0

involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• compared with control mice

tumorigenesis
• mammary gland tumor onset is earlier and tumor burden heavier than in Tg(MMTV-Erbb2)1Pv mice

integument

endocrine/exocrine glands


Mouse Genome Informatics
cn10
    Esr1tm1Sakh/Esr1tm1Sakh
Tg(MMTV-cre)4Mam/?

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• little ductal invasion of fat pad at 6 months (J:124962)
• minimal side branching (J:124962)
• mammary ductal outgrowth arrested at prepubertal stage (J:124962)

integument
• mammary ductal outgrowth arrested at prepubertal stage (J:124962)
• little ductal invasion of fat pad at 6 months (J:124962)
• minimal side branching (J:124962)


Mouse Genome Informatics
cn11
    Map2k7tm1.1Twad/Map2k7tm1.2Twad
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• mice exhibit normal mammary gland formation throughout puberty (J:170904)


Mouse Genome Informatics
cn12
    Stat3tm1Dlv/Stat3tm1Dlv
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• reduction in the proportion of IL-17-producing T cells after polyclonally stimulated for 3 days in media alone or under optimal Th17 conditions in vitro

immune system
• reduction in the proportion of IL-17-producing T cells after polyclonally stimulated for 3 days in media alone or under optimal Th17 conditions in vitro


Mouse Genome Informatics
cn13
    Ep300tm2Pkb/Ep300tm2Pkb
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• unexpectedly, no lymphomas developed for at least the first year of life (J:105505)


Mouse Genome Informatics
cn14
    Trp53tm1Brn/Trp53+
Tg(MMTV-cre)4Mam/0

involves: 129P2/OlaHsd * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 92% of mice have mammary tumors
• many mice have tumors in more than one gland
• mammary tumors are either spindle/epithelial-mesenchymal transition or poorly differentiated adenocarcinoma


Mouse Genome Informatics
cn15
    Chuktm1Yhu/Chuktm1Yhu
Tg(MMTV-cre)4Mam/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• at 1 to 5 months of age, mice begin to develop skin tumors on their faces

integument
• 3 weeks after birth
• in the dorsal epidermis
• at 1 to 5 months of age, mice begin to develop skin tumors on their faces


Mouse Genome Informatics
cn16
    Rlimtm1.1Inba/Rlimtm1.1Inba
Tg(MMTV-cre)4Mam/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• male and female mice are born in normal Mendelian ratios (J:165550)


Mouse Genome Informatics
cn17
    Gt(ROSA)26Sortm1Jus/Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo
Tg(MMTV-cre)4Mam/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• expanded long term hematopoietic stem-like cells

immune system


Mouse Genome Informatics
cn18
    Grhl3tm1Jane/Grhl3tm3.1Jane
Tg(MMTV-cre)4Mam/0

involves: 129S1/Sv * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• authors state that mice exhibit a phenotype identical to Grhl3tm1Jane/Grhl3tm3.1Jane Tg(KRT14-cre)8Brn mice
• authors state that mice exhibit a phenotype identical to Grhl3tm1Jane/Grhl3tm3.1Jane Tg(KRT14-cre)8Brn mice

tumorigenesis
• authors state that mice exhibit a phenotype identical to Grhl3tm1Jane/Grhl3tm3.1Jane Tg(KRT14-cre)8Brn mice


Mouse Genome Informatics
cn19
    Krastm4Tyj/Kras+
Tg(MMTV-cre)4Mam/0

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• submandibular gland hyperplasia is seen in mutant mice

digestive/alimentary system
• submandibular gland hyperplasia is seen in mutant mice


Mouse Genome Informatics
cn20
    Pkd1tm2Ggg/Pkd1tm2Ggg
Tg(MMTV-cre)4Mam/0

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• 60% exhibit an occasional cyst on the surface of the kidney at 10 weeks of age and 100% have kidney cysts at 20 weeks of age

liver/biliary system
• 20% exhibit an occasional cyst on the surface of the liver at 10 weeks of age and 100% have multiple hepatic cysts at 20 weeks of age

Mouse Models of Human Disease
OMIM IDRef(s)
Polycystic Kidney Disease 1; PKD1 173900 J:103719


Mouse Genome Informatics
cn21
    Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)4Mam/0

involves: 129S4/SvJae * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age (J:78415)
• delay in the normal involution process and a decrease in cell apoptosis (J:78415)
• mammary glands exhibit much larger lobules on the 13th day of pregnancy (J:78415)
• mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls (J:78415)
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age (J:78415)
• virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation (J:78415)
• mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia (J:78415)

reproductive system
• mammary glands exhibit much larger lobules on the 13th day of pregnancy (J:78415)

tumorigenesis
• develop mammary gland tumors as early as 2 months of age
• tumor incidence is increased with shortened latencies in multiparous females
• benign fibroadenomas
• pleiomorphic adenocarcinomas

integument
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age (J:78415)
• delay in the normal involution process and a decrease in cell apoptosis (J:78415)
• mammary glands exhibit much larger lobules on the 13th day of pregnancy (J:78415)
• mammary ducts grow much faster during puberty than in controls, leading to earlier occupancy of the fat pad and earlier disappearance of the terminal end buds than in controls (J:78415)
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age (J:78415)
• virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation (J:78415)
• mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia (J:78415)

Mouse Models of Human Disease
OMIM IDRef(s)
Cowden Syndrome 1; CWS1 158350 J:78415


Mouse Genome Informatics
cn22
    Brca1tm1Cxd/Brca1tm2Cxd
Trp53tm1Brd/Trp53+
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * 129S7/SvEvBrd * Black Swiss * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• by 6-8 months of age, 8 of 11 females developed mammary gland tumors that exhibited several distinct histopathologies


Mouse Genome Informatics
cn23
    Brca1tm2Cxd/Brca1tm2Cxd
Tg(MMTV-cre)4Mam/0
Trp53tm1Brd/Trp53+

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to mutants with wild-type Trp53 and also an increase in the percentage of mice with hyperplastic alveolar nodules (J:132088)

tumorigenesis
• 25% of mutants develop invasive mammary cancer when exposed to exogenous estrogen
• cancers are Esr1-negative
• mutants develop mammary gland preneoplasia that are Esr1-negative

renal/urinary system
• 25% of mutants develop ureteral obstruction 1-3 months after estrogen pellet placement

integument
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to mutants with wild-type Trp53 and also an increase in the percentage of mice with hyperplastic alveolar nodules (J:132088)

cellular
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)


Mouse Genome Informatics
cn24
    Brca1tm2Cxd/Brca1tm2Cxd
Tg(MMTV-cre)4Mam/0
Tg(MMTV-rtTA)1Lach/0
Tg(tetO-Esr1)#Paf/0
Trp53tm1Brd/Trp53+

involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mutants develop hyperplastic alveolar nodules (J:132088)

tumorigenesis
• 100% of mutants develop invasive mammary cancer
• some cancers are Esr1-negative while others are Esr1-positive
• mutants develop mammary gland preneoplasia
• some preneoplasia are Esr1-negative while others are Esr1-positive

integument
• mutants develop hyperplastic alveolar nodules (J:132088)


Mouse Genome Informatics
cn25
    Brca1tm1Cxd/Brca1tm2Cxd
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * Black Swiss * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• at pregnancy day 8.5, mammary glands are smaller than controls (J:54533)
• at pregnancy day 16.5, mammary development is incomplete with fat pads that are less than 80% filled in the most severely affected mutants (J:54533)

tumorigenesis
• 3 of 10 female mice developed mammary tumors of diverse types

endocrine/exocrine glands
• developmental defects may correlate with apoptosis observed in mutant mammary glands (J:54533)
• abnormal ductal morphogenesis was observed at lactation and involution (J:54533)
• residual alveolar structures sometimes remain in involuting mammary glands (J:54533)
• at pregnancy day 8.5, mammary glands are smaller than controls (J:54533)
• at pregnancy day 16.5, mammary development is incomplete with fat pads that are less than 80% filled in the most severely affected mutants (J:54533)

integument
• developmental defects may correlate with apoptosis observed in mutant mammary glands (J:54533)
• abnormal ductal morphogenesis was observed at lactation and involution (J:54533)
• residual alveolar structures sometimes remain in involuting mammary glands (J:54533)
• at pregnancy day 8.5, mammary glands are smaller than controls (J:54533)
• at pregnancy day 16.5, mammary development is incomplete with fat pads that are less than 80% filled in the most severely affected mutants (J:54533)


Mouse Genome Informatics
cn26
    Stat5a/Stat5btm2Mam/Stat5a/Stat5btm2Mam
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * Black Swiss * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)
• the number of tertiary branches is severely decreased, the lobular units are absent, and at parturition the alveolar compartment is missing (J:92770)
• treatment with estrogen and progesterone induces very little side branching in mammary epithelia unlike in wild-type females (J:92770)

integument
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)
• the number of tertiary branches is severely decreased, the lobular units are absent, and at parturition the alveolar compartment is missing (J:92770)
• treatment with estrogen and progesterone induces very little side branching in mammary epithelia unlike in wild-type females (J:92770)

behavior/neurological
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)


Mouse Genome Informatics
cn27
    Stat5a/Stat5btm2Mam/Stat5a/Stat5btm2Mam
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * Black Swiss * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)
• the number of tertiary branches is severely decreased, the lobular units are absent, and at parturition the alveolar compartment is missing (J:92770)
• treatment with estrogen and progesterone induces very little side branching in mammary epithelia unlike in wild-type females (J:92770)

integument
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)
• the number of tertiary branches is severely decreased, the lobular units are absent, and at parturition the alveolar compartment is missing (J:92770)
• treatment with estrogen and progesterone induces very little side branching in mammary epithelia unlike in wild-type females (J:92770)

behavior/neurological
• 10 out of 12 dams were unable to secrete milk, while the remaining 2 could secrete only small amounts of milk (J:92770)


Mouse Genome Informatics
cn28
    Sav1tm1.1Rjo/Sav1tm1.1Rjo
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * C57BL/6 * CD-1 * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• by 14 months of age


Mouse Genome Informatics
cn29
    Brca1tm2Cxd/Brca1tm2Cxd
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)
• dense mammary epithelial cell growth is seen in estrogen-treated intact and ovariectomized mutants but not wild-type mice (J:132088)
• mammary glands exhibit longer ductal extension during puberty (6 weeks of age) (J:132088)
• 3 week old mutants exposed to continuous exogenous estrogen and progesterone for 2 weeks exhibit impaired terminal end bud differentiation into terminal ductal ends unlink wild-type mice (J:132088)
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to controls and also an increase in the percentage of mice with hyperplastic alveolar nodules (J:132088)

integument
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)
• dense mammary epithelial cell growth is seen in estrogen-treated intact and ovariectomized mutants but not wild-type mice (J:132088)
• mammary glands exhibit longer ductal extension during puberty (6 weeks of age) (J:132088)
• 3 week old mutants exposed to continuous exogenous estrogen and progesterone for 2 weeks exhibit impaired terminal end bud differentiation into terminal ductal ends unlink wild-type mice (J:132088)
• mutants exposed to estrogen exhibit an increase in the number of hyperplastic alveolar nodules per mammary gland compared to controls and also an increase in the percentage of mice with hyperplastic alveolar nodules (J:132088)

renal/urinary system
• 71% of mutants develop ureteral obstruction 1-5 months after estrogen pellet placement

tumorigenesis
• 14% of mutants develop invasive mammary cancer when exposed to exogenous estrogen

cellular
• mutants exhibit increased mammary epithelial cellular proliferation compared to controls when treated with exogenous estrogen (J:132088)
• dense mammary epithelial cell growth is seen in estrogen-treated intact and ovariectomized mutants but not wild-type mice (J:132088)


Mouse Genome Informatics
cn30
    Mnttm1Awb/Mnttm1.1Awb
Tg(MMTV-cre)4Mam/?

involves: 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• in 7 of 11 continuously mated females with tumor latency ranging from 6 to 24 months compared to control mice that do not develop tumors some tumors show lymphocyte invasion
• tumors are invasive carcinomas that include solid tubular carcinomas, tubular carcinomas and carcinomas with sarcomatous changes
• tumors display ductal enlargement that may or may not be pre-existing

endocrine/exocrine glands
• involution is delayed at I2, I5, and I16 (J:110115)
• apoptosis levels peak at day 5 of involution compared to day 2 in wild-type mice (J:110115)
• apoptosis in the alveoli and ducts is delayed and fewer cells undergo apoptosis (J:110115)
• during involution after weaning, mice display enlarged ducts (J:110115)
• after involution ducts remain enlarged (J:110115)
• nonvirgin females exhibit 90% enlarged ducts compared to 40% in nonvirgin control mice and virgin mice exhibit 50% enlarged ducts compared to 30% in virgin control mice (J:110115)

integument
• involution is delayed at I2, I5, and I16 (J:110115)
• apoptosis levels peak at day 5 of involution compared to day 2 in wild-type mice (J:110115)
• apoptosis in the alveoli and ducts is delayed and fewer cells undergo apoptosis (J:110115)
• during involution after weaning, mice display enlarged ducts (J:110115)
• after involution ducts remain enlarged (J:110115)
• nonvirgin females exhibit 90% enlarged ducts compared to 40% in nonvirgin control mice and virgin mice exhibit 50% enlarged ducts compared to 30% in virgin control mice (J:110115)


Mouse Genome Informatics
cn31
    Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan/Gt(ROSA)26Sor+
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival time is increased compared to mutant mice carrying Tg(MMTV-cre)1Mam

tumorigenesis
• develop a less diverse set of tumors compared to mutant mice carrying Tg(MMTV-cre)1Mam
• start to develop by 5 months of age in both virgin and multiparous mice
• 69% of mice have palpable mammary tumors at the time of death
• tumors are typically either adenosquamous carcinoma or adenomyoepithioma
• isolated lung metastases are seen in rare cases

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:170898


Mouse Genome Informatics
cn32
    Gt(ROSA)26Sortm2(Pik3ca)Egan/Gt(ROSA)26Sor+
Tg(MMTV-cre)4Mam/0

involves: 129S6/SvEvTac * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype


Mouse Genome Informatics
cn33
    Ctnna1tm1Efu/Ctnna1tm1Efu
Tg(MMTV-cre)4Mam/?

involves: 129X1/SvJ * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mammary glands have reduced numbers of epithelial cells (J:87469)
• some epithelial cells remain condensed and disorganized without forming alveolar structures (J:87469)
• lumens are absent from clusters of epithelium (J:87469)
• milk proteins are reduced (J:87469)
• apoptosis in mammary epithelium is increased (J:87469)

integument
• mammary glands have reduced numbers of epithelial cells (J:87469)
• some epithelial cells remain condensed and disorganized without forming alveolar structures (J:87469)
• lumens are absent from clusters of epithelium (J:87469)
• milk proteins are reduced (J:87469)
• apoptosis in mammary epithelium is increased (J:87469)
• occasionally hair development is not on schedule


Mouse Genome Informatics
cn34
    Ppargtm1Gonz/Ppargtm1Gonz
Tg(MMTV-cre)4Mam/?

involves: 129X1/SvJ * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• mice have normal mammary gland development (J:76553)


Mouse Genome Informatics
cn35
    Elf5tm1Sin/Elf5tm1Sin
Tg(MMTV-cre)4Mam/0

involves: C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• the expected number of mice are born but very few survive, no time of lethality provided

endocrine/exocrine glands
• surviving females display poorly developed mammary epithelial structures (J:148362)
• surviving females display severe lactation defects (J:148362)

integument
• surviving females display poorly developed mammary epithelial structures (J:148362)
• surviving females display severe lactation defects (J:148362)


Mouse Genome Informatics
cn36
    Gt(ROSA)26Sortm1Jus/Gt(ROSA)26Sor+
Tg(MMTV-cre)4Mam/0

involves: C57BL/6J * C57BL/6N * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 64 days

immune system
• in diseased mice
• lymphoid infiltration in the thymus at 6 months
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months
• in the spleen
• immature single positive cells in the thymus
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months
• nearly all B cells are arrested in the early pro-B stage
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months
• in diseased mice
• in diseased mice
• lymphoid infiltration in the spleen, interstitial and perivascular space of the kidney, perivascular cuffs in the liver, meninges surrounding the brain, thymus, stomach and intestine at 6 months
• lymphoid infiltration in the intestine at 6 months
• lymphoid infiltration in the stomach at 6 months
• lymphoid infiltration in the meninges surrounding the brain at 6 months
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months

digestive/alimentary system
• lymphoid infiltration in the intestine at 6 months
• lymphoid infiltration in the stomach at 6 months

tumorigenesis
• mice rapidly develop and succumb to acute leukemia

behavior/neurological

growth/size
• in diseased mice

respiratory system

liver/biliary system
• lymphoid infiltration in the perivascular cuffs in the liver at 6 months
• in diseased mice

nervous system
• lymphoid infiltration in the meninges surrounding the brain at 6 months

renal/urinary system
• lymphoid infiltration in the interstitial and perivascular space of the kidney at 6 months
• in diseased mice

hematopoietic system
• in diseased mice
• lymphoid infiltration in the thymus at 6 months
• slightly at 6 months
• severely at 6 months
• monomorphic, enlarged white blood cells with a high nuclear:chromatin ratio (consistent with leukemic blasts) at 6 months
• in the spleen
• immature single positive cells in the thymus
• large, unstained cells (abnormal blasts) in the peripheral blood at 6 months
• nearly all B cells are arrested in the early pro-B stage
• disrupted separation between white and red pulp by infiltrating lymphoblasts at 6 months
• in diseased mice

endocrine/exocrine glands
• in diseased mice
• lymphoid infiltration in the thymus at 6 months


Mouse Genome Informatics
cn37
    Mnttm1Phu/Mnttm1Phu
Tg(MMTV-cre)4Mam/?

involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• developed in 6 out of 10 females tested
• tumor latency ranged from 6 months to 20 months


Mouse Genome Informatics
cx38
    Brca1tm2Cxd/Brca1tm2Cxd
Pkmtm1.1Mgvh/Pkmtm1.1Mgvh
Tg(MMTV-cre)4Mam/0
Trp53tm1Brd/Trp53+

involves: 129S4/SvJaeSor * 129S6/SvEvTac * 129S7/SvEvBrd * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• accelerated tumor associated mortality relative to control mice

tumorigenesis
• liver metastases observed in 3/5 mice as compared to 0/7 relative to control mice
• mice develop breast tumors similar to control mice
• liver metastases observed in 3/5 mice as compared to 0/7 relative to control mice


Mouse Genome Informatics
tg39
    Tg(MMTV-cre)4Mam/?
involves: FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
other phenotype
• 81% of pups nursed by mothers carrying this transgene survive to weaning
• pups nursed by mothers carrying this transgene are smaller than those nursed by control mothers but not statistically

endocrine/exocrine glands
• mammary gland development checked at the end of lactation was highly variable among mice (J:168531)
• cre expression as determined using Gt(ROSA)26Sortm1Sor as a reporter was not initiated until about 3 weeks of age (J:168531)
• cre expression shows a high level of mosaicism initially but complete deletion was observed in older mice (J:168531)

integument
• mammary gland development checked at the end of lactation was highly variable among mice (J:168531)
• cre expression as determined using Gt(ROSA)26Sortm1Sor as a reporter was not initiated until about 3 weeks of age (J:168531)
• cre expression shows a high level of mosaicism initially but complete deletion was observed in older mice (J:168531)