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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Ptentm1Hwu
targeted mutation 1, Hong Wu
MGI:2156086
Summary 144 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
ht1
Ptentm1Hwu/Pten+ involves: 129S4/SvJae * BALB/c MGI:3707147
cn2
Ptentm1Hwu/Ptentm1Hwu involves: 129S4/SvJae MGI:4848150
cn3
Kdrtm1Jrt/Kdr+
Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+
B6.129-Twist2tm1.1(cre)Dor Kdrtm1Jrt Ptentm1Hwu MGI:5503216
cn4
Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+
B6.129-Twist2tm1.1(cre)Dor Ptentm1Hwu MGI:5503192
cn5
Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-icre)5092Coo/0
B6.Cg-Ptentm1Hwu Tg(Gdf9-icre)5092Coo MGI:4839213
cn6
Ptentm1Hwu/Pten+
Tg(Nkx2-1-cre)2Sand/0
B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand MGI:5517709
cn7
Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0
B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand MGI:5517706
cn8
Ptentm1Hwu/Ptentm1Hwu
Tg(Tyr-cre)1Lru/0
B6.Cg-Ptentm1Hwu Tg(Tyr-cre)1Lru MGI:4882033
cn9
Ptentm1Hwu/Ptentm1Hwu
Tg(Zp3-cre)93Knw/0
B6.Cg-Ptentm1Hwu Tg(Zp3-cre)93Knw MGI:4882031
cn10
Ptentm1Hwu/Ptentm1Hwu
Rfwd2tm2.1Vmd/Rfwd2tm2.1Vmd
Tg(Pbsn-cre)4Prb/0
B6N.Cg-Rfwd2tm2.1Vmd Ptentm1Hwu Tg(Pbsn-cre)4Prb MGI:5013604
cn11
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
BKS.Cg-Ptprcb Thy1a Tg(Mx1-cre)1Cgn Ptentm1Hwu MGI:4839500
cn12
Pik3catm1Jjz/Pik3catm1Jjz
Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
FVB.Cg-Pik3catm1Jjz Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr MGI:5506907
cn13
Pik3catm1Jjz/Pik3catm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
FVB.Cg-Pik3catm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr MGI:5506905
cn14
Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
FVB.Cg-Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr MGI:5506906
cn15
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
FVB.Cg-Ptentm1Hwu Tg(KRT14-cre)#Smr MGI:5506904
cn16
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Ptentm1Hwu/Ptentm1Hwu
involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N MGI:5460854
cn17
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
involves: 129 * 129S4/SvJae * BALB/c * C57BL/6 MGI:4847601
cn18
Ptentm1Hwu/Ptentm1Hwu
Tgfbr1tm1.1Karl/Tgfbr1tm1.1Karl
Tg(KRT14-cre/ERT)20Efu/0
involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N MGI:5487550
cn19
Hspa5tm1Alee/Hspa5tm1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2 MGI:4943513
cn20
Hspa5tm1Alee/Hspa5+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2 MGI:4943514
cn21
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2 MGI:3805865
cn22
Hspa5tm1Alee/Hspa5tm1.1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2 MGI:4943512
cn23
Ptentm1Hwu/Ptentm1Hwu
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0
involves: 129 * 129S4/SvJae * C57BL/6 * FVB/N MGI:4882116
cn24
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn
involves: 129 * C57BL/6 MGI:3813634
cn25
Cd19tm1(cre)Cgn/Cd19+
Inpp5dtm1Rav/Inpp5dtm1Rav
Ptentm1Hwu/Ptentm1Hwu
involves: 129P2/OlaHsd * 129S4/SvJae MGI:5013951
cn26
Ptentm1Hwu/Ptentm1Hwu
Lyz2tm1(cre)Ifo/Lyz2+
involves: 129P2/OlaHsd * 129S4/SvJae MGI:4836609
cn27
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
involves: 129P2/OlaHsd * 129S4/SvJae MGI:4829791
cn28
Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn
Ptentm1Hwu/Ptentm1Hwu
involves: 129P2/OlaHsd * 129S4/SvJae MGI:4829792
cn29
Braftm1Mmcm/Braftm1Mmcm
Nkx3-1tm4(cre/ERT2)Mms/Nkx3-1+
Ptentm1Hwu/Pten+
involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6 MGI:5543907
cn30
Ptentm1Hwu/Ptentm1Hwu
Trp53tm2.1Tyj/Trp53+
Amhr2tm3(cre)Bhr/Amhr2+
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd MGI:5704372
cn31
Dicer1tm1Tara/Dicer1tm1Tara
Ptentm1Hwu/Ptentm1Hwu
Amhr2tm3(cre)Bhr/Amhr2+
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd MGI:5704363
cn32
Dicer1tm1Tara/Dicer1tm1Tara
Ptentm1Hwu/Ptentm1Hwu
Trp53tm2.1Tyj/Trp53+
Amhr2tm3(cre)Bhr/Amhr2+
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd MGI:5704370
cn33
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 MGI:5007685
cn34
Ptentm1Hwu/Ptentm1Hwu
Rps6kb1tm1Gtho/Rps6kb1tm1Gtho
Tg(Mx1-cre)1Cgn/0
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA MGI:4944270
cn35
Akt2tm1.1Mbb/Akt2tm1.1Mbb
Ptentm1Hwu/Ptentm1Hwu
Tg(Alb-cre)21Mgn/0
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA MGI:4838529
cn36
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB MGI:3844324
cn37
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(GFAP-cre)25Mes/0
Trp53tm1Tyj/Trp53+
involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4840094
cn38
Errfi1tm1Jwj/Errfi1tm1Jwj
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4944273
cn39
Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-Bgeo/ALPP)1Lbe/0
Tg(Ela1-cre/ERT)1Dam/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4836240
cn40
Ptentm1Hwu/Ptentm1Hwu
Cnptm1(cre)Kan/Cnp+
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4836647
cn41
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4839214
cn42
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4839216
cn43
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ MGI:4944272
cn44
Ctnnb1tm2Kem/Ctnnb1tm2Kem
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N MGI:4839561
cn45
Ctnnb1tm2Kem/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N MGI:4839562
cn46
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd MGI:4849443
cn47
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 MGI:3813633
cn48
Artm1Verh/Y
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2 MGI:5009703
cn49
Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)7Mul/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4839510
cn50
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Trp53tm1Elee/Trp53+
Tg(GFAP-cre)25Mes/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4840096
cn51
Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Pten+
Tg(MMTV-cre)7Mul/0
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4839508
cn52
Bcl2l11tm1.1Ast/Bcl2l11+
Ptentm1Hwu/Pten+
Tg(CD2-icre)4Kio/0
involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca MGI:3783573
cn53
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0
Trp53tm1Tyj/Trp53tm1Tyj
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 * CBA MGI:4836239
cn54
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp1-cre)1Jig/0
involves: 129S2/SvPas * 129S4/SvJae * FVB/N MGI:4844100
cn55
Ptentm1Hwu/Ptentm1Hwu
Tg(CYP19A1-cre)1Jri/0
involves: 129S4/SvJae MGI:4847591
cn56
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)#Tfln/0
involves: 129S4/SvJae MGI:5688693
cn57
Ptentm1Hwu/Ptentm1Hwu
Tg(Cr2-cre)3Cgn/0
involves: 129S4/SvJae MGI:4430559
cn58
Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp4-cre)1Abel/0
involves: 129S4/SvJae MGI:4830361
cn59
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae MGI:5014516
cn60
Fastm1Ach/Fastm1Ach
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae MGI:5014515
cn61
Ptentm1Hwu/Ptentm1Hwu
Rictortm1.1Mgn/Rictortm1.1Mgn
involves: 129S4/SvJae * 129S6/SvEvTac MGI:4848147
cn62
Ptentm1Hwu/Ptentm1Hwu
Rictortm1.1Mgn/Rictortm1.1Mgn
Tg(Ins2-cre)25Mgn/0
involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA MGI:5008147
cn63
Nkx3-1tm4(cre/ERT2)Mms/Nkx3-1+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 MGI:4365721
cn64
Ptentm1Hwu/Ptentm1Hwu
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Alb1-cre)1Dlr/0
involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N MGI:4839217
cn65
Ptentm1Hwu/Ptentm1Hwu
Amhr2tm3(cre)Bhr/Amhr2+
involves: 129S4/SvJae * 129S7/SvEvBrd MGI:4942351
cn66
Amhr2tm3(cre)Bhr/Amhr2+
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ MGI:4941746
cn67
Amhr2tm3(cre)Bhr/Amhr2+
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 MGI:5432232
cn68
Amhr2tm3(cre)Bhr/Amhr2+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 MGI:5013567
cn69
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(CYP19A1-cre)1Jri/0
involves: 129S4/SvJae * 129X1/SvJ * C57BL/6 MGI:5432226
cn70
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(Upk2-cre)6Xrw/0
involves: 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4943270
cn71
Ctnnb1tm1Mmt/Ctnnb1tm1Mmt
Ptentm1Hwu/Ptentm1Hwu
Tg(Upk2-cre)6Xrw/0
involves: 129S4/SvJae * 129X1/SvJ * FVB/N MGI:4943268
cn72
Ptentm1Hwu/Pten+
Tg(Nkx2-1-cre)2Sand/0
involves: 129S4/SvJae * BALB/c * C57BL/6 MGI:5517675
cn73
Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0
involves: 129S4/SvJae * BALB/c * C57BL/6 MGI:5014514
cn74
Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Pdx1-cre)89.1Dam/0
involves: 129S4/SvJae * BALB/c * C57BL/6 MGI:5013916
cn75
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA MGI:5013917
cn76
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA MGI:5008144
cn77
Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-fat-1)1Jxk/0
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2 MGI:4847617
cn78
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2 MGI:4420974
cn79
Ptentm1Hwu/Pten+
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2 MGI:4420975
cn80
Ptentm1Hwu/Pten+
Tg(ARR2/Pbsn-FGF8)3Prb/0
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2 MGI:4843916
cn81
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0
involves: 129S4/SvJae * BALB/c * C57BL/6 * FVB/N MGI:4839560
cn82
Ptentm1Hwu/Ptentm1Hwu
Tg(Camk2a-cre)T50Stl/0
Tg(Thy1-EGFP)MJrs/0
involves: 129S4/SvJae * BALB/c * C57BL/6J * CBA MGI:4942301
cn83
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh16-cre)91Igr/0
involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR MGI:4943546
cn84
Ptentm1Hwu/Ptentm1Hwu
Vhltm1Jae/Vhltm1Jae
Tg(Cdh16-cre)91Igr/0
involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR MGI:4943534
cn85
Ptentm1Hwu/Ptentm1Hwu
Tg(Vil-cre)997Gum/0
involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL MGI:4941760
cn86
ApcMin/Apc+
Ptentm1Hwu/Ptentm1Hwu
Tg(Vil-cre)997Gum/0
involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL MGI:4941759
cn87
Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0
involves: 129S4/SvJae * BALB/c * C57BL/6NHsd MGI:4849441
cn88
Ptentm1Hwu/Ptentm1Hwu
Tg(Gfap-cre)77.6Mvs/0
involves: 129S4/SvJae * BALB/c * C57BL/6NHsd MGI:3838843
cn89
Ptentm1Hwu/Ptentm1Hwu
Slc6a3tm1.1(cre)Bkmn/Slc6a3+
involves: 129S4/SvJae * C57BL/6 MGI:4849440
cn90
Gt(ROSA)26Sortm9(cre/ESR1)Arte/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * C57BL/6 MGI:5008585
cn91
Ptentm1Hwu/Ptentm1Hwu
Tg(Scgb1a1-cre)1Tauc/0
involves: 129S4/SvJae * C57BL/6 MGI:4943565
cn92
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Scgb1a1-cre)1Tauc/0
involves: 129S4/SvJae * C57BL/6 MGI:4943568
cn93
Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sortm9(cre/ESR1)Arte
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * C57BL/6 MGI:5008587
cn94
Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0
involves: 129S4/SvJae * C57BL/6 MGI:4836606
cn95
Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-icre)5092Coo/0
involves: 129S4/SvJae * C57BL/6 MGI:4882032
cn96
Pkn3tm1.1Mrl/Pkn3tm1.1Mrl
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca MGI:5688869
cn97
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca MGI:5688871
cn98
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA MGI:5007630
cn99
Mirc14tm1.1Flv/Mirc14tm1.1Flv
Ptentm1Hwu/Ptentm1Hwu
Tg(Cd4-cre)1Cwi/0
involves: 129S4/SvJae * C57BL/6 * C57BL/6N * DBA/2 * SJL MGI:5529025
cn100
Leprdb/Leprdb
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0
involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA MGI:5013485
cn101
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0
involves: 129S4/SvJae * C57BL/6 * CBA MGI:4836237
cn102
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJae * C57BL/6 * CBA MGI:4836620
cn103
Apctm1Tno/Apctm1Tno
Ptentm1Hwu/Ptentm1Hwu
Tg(Cyp1a1-cre/ERT)1Dwi/0
involves: 129S4/SvJae * C57BL/6 * CBA MGI:4943267
cn104
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre/Esr1*)35.10Dam/0
involves: 129S4/SvJae * C57BL/6 * CBA MGI:4836238
cn105
Pkn3tm1.1Mrl/Pkn3tm1.1Mrl
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJae * C57BL/6 * CBA/J MGI:5688867
cn106
Pkn3tm1.1Mrl/Pkn3+
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
involves: 129S4/SvJae * C57BL/6 * CBA/J MGI:5688868
cn107
Ptentm1Hwu/Ptentm1Hwu
Tg(Alb-cre)21Mgn/0
involves: 129S4/SvJae * C57BL/6 * DBA MGI:4829790
cn108
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0
involves: 129S4/SvJae * C57BL/6 * DBA MGI:4839070
cn109
Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5008586
cn110
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:4358249
cn111
Ptentm1Hwu/Pten+
Tmprss2tm2.1(ETV1)Sho/Tmprss2tm2.1(ETV1)Sho
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5578649
cn112
Ergtm1.1Sho/Ergtm1.1Sho
Ptentm1Hwu/Ptentm1Hwu
Tmprss2tm3Sho/Tmprss2tm3Sho
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5578652
cn113
Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5705328
cn114
Ptentm1Hwu/Ptentm1Hwu
Tg(Plp1-cre/ERT2)1Ueli/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:4837112
cn115
Gt(ROSA)26Sortm2(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5008589
cn116
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
involves: 129S4/SvJae * C57BL/6 * DBA/2 MGI:5705321
cn117
Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-icre)5092Coo/?
involves: 129S4/SvJae * C57BL/6J MGI:4941739
cn118
Pdpk1tm1Maka/Pdpk1tm1Maka
Ptentm1Hwu/Ptentm1Hwu
Tg(Zp3-cre)93Knw/0
involves: 129S4/SvJae * C57BL/6J MGI:5013920
cn119
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae * C57BL/6J MGI:4836596
cn120
Ptentm1Hwu/Ptentm1Hwu
Tsc1tm1Djk/Tsc1tm1Djk
Tg(Gdf9-icre)5092Coo/?
involves: 129S4/SvJae * C57BL/6J MGI:4941741
cn121
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
involves: 129S4/SvJae * C57BL/6J * SJL/J MGI:3813525
cn122
Ptentm1Hwu/Pten+
Tg(KRT14-cre)#Smr/0
involves: 129S4/SvJae * C57BL/6J * SJL/J MGI:3813526
cn123
Ptentm1Hwu/Ptentm1Hwu
Tg(Ckmm-cre)5Khn/?
involves: 129S4/SvJae * FVB MGI:4944271
cn124
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)4Mam/0
involves: 129S4/SvJae * FVB MGI:4829793
cn125
Ptentm1Hwu/Ptentm1Hwu
Tg(Ddx4-cre)1Dcas/0
involves: 129S4/SvJae * FVB/N MGI:4882148
cn126
Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp1-cre)1Jig/0
involves: 129S4/SvJae * FVB/N MGI:4844083
cn127
Ptentm1Hwu/Ptentm1Hwu
Tg(GZMB-cre)1Jcb/0
involves: 129S4/SvJae * FVB/N MGI:5013915
cn128
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)7Mul/0
involves: 129S4/SvJae * FVB/N MGI:4839512
cn129
Ptentm1Hwu/Ptentm1Hwu
Tg(Alb1-cre)1Dlr/0
involves: 129S4/SvJae * FVB/N MGI:4839218
cn130
Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Upk2-cre)6Xrw/0
involves: 129S4/SvJae * FVB/N MGI:5141742
cn131
Ptentm1Hwu/Ptentm1Hwu
Tg(Myh6-cre/Esr1*)1Jmk/0
involves: 129S4/SvJae * FVB/N MGI:4882047
cn132
Ptentm1Hwu/Ptentm1Hwu
Tg(GFAP-cre)25Mes/0
involves: 129S4/SvJae * FVB/N MGI:4830362
cn133
Ptentm1Hwu/Ptentm1Hwu
Tg(Nes-cre)1Atp/0
involves: 129S4/SvJae * FVB/N MGI:4829794
cn134
Ptentm1Hwu/Ptentm1Hwu
Tg(Ddx4-cre/ERT2)1Dcas/0
involves: 129S4/SvJae * FVB/N MGI:4882150
cn135
Ptentm1Hwu/Ptentm1Hwu
Tg(TPO-cre)1Shk/0
involves: 129S4/SvJae * FVB/NCr MGI:5294347
cn136
Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0
Tg(TPO-cre)1Shk/0
involves: 129S4/SvJae * FVB/NCr * FVB/NJ MGI:5294346
cn137
Ptentm1Hwu/Ptentm1Hwu
Vhltm1Jae/Vhltm1Jae
Tg(Cdh16-cre)91Igr/0
involves: 129S4/SvJae * ICR MGI:4839497
cn138
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh16-cre)91Igr/0
involves: 129S4/SvJae * ICR MGI:4839499
cn139
Gt(ROSA)26Sortm2Thl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Tyrc-Brd/Tyrc-Brd
involves: 129/Sv * 129S4/SvJae * C57BL/6 MGI:5008633
cn140
Gt(ROSA)26Sortm2Thl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Thl/Trp53tm1Thl
Tyrc-Brd/Tyrc-Brd
involves: 129/Sv * 129S4/SvJae * C57BL/6 MGI:5008634
cn141
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm1(CAG-EGFR)Char/Col1a1tm1(CAG-EGFR)Char
Ptentm1Hwu/Ptentm1Hwu
involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL MGI:3837855
cn142
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm1(CAG-EGFR)Char/Col1a1tm2(CAG-EGFR*)Char
Ptentm1Hwu/Ptentm1Hwu
involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL MGI:3837857
cn143
Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm2(CAG-EGFR*)Char/Col1a1tm2(CAG-EGFR*)Char
Ptentm1Hwu/Ptentm1Hwu
involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL MGI:3837856
cx144
Pik3catm1.1Waph/Pik3ca+
Ptentm1Hwu/Ptentm1Hwu
involves: 129S1/Sv * 129S4/SvJae * BALB/c * C57BL/6 MGI:5427585


Genotype
MGI:3707147
ht1
Allelic
Composition
Ptentm1Hwu/Pten+
Genetic
Background
involves: 129S4/SvJae * BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Ptentm1.1Hwu on the BALB/c background in the first seven months




Genotype
MGI:4848150
cn2
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

endocrine/exocrine glands
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

tumorigenesis
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age

muscle
• primary myotube cultures treated with adenovirus-cre to delete Pten results in increased myotube size
• primary myotube cultures treated with adenovirus-cre do not exhibit the palmitate-induced decrease in cell size seen in control myotubes

homeostasis/metabolism
• mice injected neonatally with a cre-expressing adenovirus into the sensorimotor cortex and undergoing pyramidotomy in adulthood exhibit an increase in trans-midline sprouting of adult corticospinal tract axons compared to controls
• neonatal and postnatal deletion of Pten by injecting cre-expressing adenovirus into the sensorimotor cortex at the neonatal stage or 4 weeks of age, respectively, results in increased corticospinal tract regeneration following T8 complete spinal cord crush injury compared to controls
• the increase in corticospinal tract regeneration is seen when complete spinal cord crush is done at 2 and 5 months of age and the regenerating axons follow ectopic trajectories and extend bilaterally in contrast with normal unilateral extension in controls
• regenerating corticospinal tract axons after injury from mice injected with cre-expressing adenovirus are able to reform synaptic structures in the spinal cord caudal to the lesion site




Genotype
MGI:5503216
cn3
Allelic
Composition
Kdrtm1Jrt/Kdr+
Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+
Genetic
Background
B6.129-Twist2tm1.1(cre)Dor Kdrtm1Jrt Ptentm1Hwu
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdrtm1Jrt mutation (2 available); any Kdr mutation (34 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Twist2tm1.1(cre)Dor mutation (1 available); any Twist2 mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Defect in angioblast differentiation in Ptentm1Hwu/Ptentm1Hwu Kdrtm1Jrt/Kdr+ Twist2tm1.1(cre)Dor/Twist2+ mice

cardiovascular system
• vasculogenesis defect
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels

respiratory system
• increase in angioblasts in E18.5 lungs




Genotype
MGI:5503192
cn4
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+
Genetic
Background
B6.129-Twist2tm1.1(cre)Dor Ptentm1Hwu
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Twist2tm1.1(cre)Dor mutation (1 available); any Twist2 mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Increase in mesenchymal cell proliferation in Ptentm1Hwu/Ptentm1Hwu Twist2tm1.1(cre)Dor/Twist2+ mice

mortality/aging
• mutants with less severe phenotypes die within 2-3 hours of birth, displaying cyanosis, chest retractions, and dyspnea

respiratory system
• increase in collagen deposition in the lungs
• alveolar spaces are frequently lined by cuboidal cells with immature lamellar bodies
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
• marker analysis indicates expansion of the distal epithelial progenitor cell domain
• E18.5 lungs exhibit a hypercellular mesenchymal compartment
• more than 5-fold increase in the number of CD45-CD31+ embryonic mesenchymal progenitor side population (E-SP) and CD45-CD31- E-SP cell populations in E17.5 lungs indicating an increase in lung mesenchymal progenitor cell populations
• in mutants with less severe phenotypes that die within hours of birth

cardiovascular system
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
• 44% of embryos lack of vascularization in entire embryos at E15.5
• E15.5 embryos show lack of vascularization in organs such as limbs and liver
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels
• 15% of embryos exhibit hemorrhage at E18.5

homeostasis/metabolism
• newborns show a decrease in blood oxygenation
• in mutants with less severe phenotypes that die within hours of birth




Genotype
MGI:4839213
cn5
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-icre)5092Coo/0
Genetic
Background
B6.Cg-Ptentm1Hwu Tg(Gdf9-icre)5092Coo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Gdf9-icre)5092Coo mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells
• follicular structure at 12 weeks of age is deformed and luteolysis is observed
• reduction in follicle death and clearance before and around the time of sexual maturity
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)
• by p23, no primordial follicles an be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage
• at P8, ovaries appear larger with more activated follicles
• by P23 and 35, ovaries remain larger and contain more activated follicles

homeostasis/metabolism
• increase in levels of follicle-stimulating hormone at 12-20-week old females
• increase in levels of luteinizing hormone at 12-20-week old females

reproductive system
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells
• follicular structure at 12 weeks of age is deformed and luteolysis is observed
• reduction in follicle death and clearance before and around the time of sexual maturity
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%)
• by p23, no primordial follicles an be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage
• at P8, ovaries appear larger with more activated follicles
• by P23 and 35, ovaries remain larger and contain more activated follicles
• accelerated oocyte growth
• many transient follicles contain degraded oocytes
• females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure
• many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia
• older females exhibit irregular estrous cycles
• females become infertile in early adulthood, after 12-13 weeks of age




Genotype
MGI:5517709
cn6
Allelic
Composition
Ptentm1Hwu/Pten+
Tg(Nkx2-1-cre)2Sand/0
Genetic
Background
B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Nkx2-1-cre)2Sand mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage
• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

homeostasis/metabolism
• P14 mutants show a mild decrease of T4 but normal TSH

tumorigenesis
• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age




Genotype
MGI:5517706
cn7
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0
Genetic
Background
B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Nkx2-1-cre)2Sand mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• at P14, thyroid architecture is altered, with multilayered epithelial cells surrounding the colloid lumen and with some dysmorphic follicles containing abnormal material inside
• dysmorphic follicles containing abnormal material inside and multiple degenerative follicles which have varying degrees of colloid depletion are seen at P14
• increase in thyroid size is already seen at E15.5 and is striking by P14
• increase in epithelial cell proliferation rate at E15.5 and P14
• Background Sensitivity: at P14, epithelial cell proliferation rates are higher on the congenic C57BL/6 background than on the BALB/c background
• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma

homeostasis/metabolism
• decrease in T4 hormonal levels at P14

mortality/aging
• all mutants die before 2 weeks of age due to compression of the trachea and esophagus by the enlarged thyroid

tumorigenesis
• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma




Genotype
MGI:4882033
cn8
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Tyr-cre)1Lru/0
Genetic
Background
B6.Cg-Ptentm1Hwu Tg(Tyr-cre)1Lru
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Tyr-cre)1Lru mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• die between 13 and 20 days after birth

growth/size/body
• although mutants are similar in weight and size as wild-type mice on P2, they fail to gain as much weight over the next 20 days as controls

digestive/alimentary system
• mutants exhibit some intraluminal bubbles along the gastrointestinal tract
• mutants exhibit intestinal pseudoobstruction
• dilatation of the cecum
• mutants exhibit intestinal pseudoobstruction

nervous system
• hypertrophy and hyperplasia of the myenteric and submucosal plexus in the enteric nervous system by 2 weeks of age resulting in ganglioneuromatosis
• enteric ganglia are bigger than in wild-type at P15
• hyperplasia is observed in enteric neuronal cells at E17.5 while hypertrophy of enteric neuronal cells is only seen after birth and not during embryonic development

pigmentation
• hyperpigmentation in the tail, pinna, paws, skin, and olfactory bulb




Genotype
MGI:4882031
cn9
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Zp3-cre)93Knw/0
Genetic
Background
B6.Cg-Ptentm1Hwu Tg(Zp3-cre)93Knw
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Zp3-cre)93Knw mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• mice exhibit normal follicular development, showing healthy corpora lutea and preovulatory follicles at 16 weeks of age, normal resumption of meiosis, ovulation, fertilization and fertility, although PI3K-Akt signaling is elevated




Genotype
MGI:5013604
cn10
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Rfwd2tm2.1Vmd/Rfwd2tm2.1Vmd
Tg(Pbsn-cre)4Prb/0
Genetic
Background
B6N.Cg-Rfwd2tm2.1Vmd Ptentm1Hwu Tg(Pbsn-cre)4Prb
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Rfwd2tm2.1Vmd mutation (0 available); any Rfwd2 mutation (17 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• invasive in 11 of 13 mice at 30 weeks of age
• high grade in 2 of 13 mice at 30 weeks of age

endocrine/exocrine glands
• invasive in 11 of 13 mice at 30 weeks of age
• high grade in 2 of 13 mice at 30 weeks of age

tumorigenesis
• invasive in 11 of 13 mice at 30 weeks of age
• high grade in 2 of 13 mice at 30 weeks of age




Genotype
MGI:4839500
cn11
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0
Genetic
Background
BKS.Cg-Ptprcb Thy1a Tg(Mx1-cre)1Cgn Ptentm1Hwu
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Mx1-cre)1Cgn mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mutants become ill shortly after pIpC treatment and exhibit lethargy, ruffling of fur, and hunched posture and die from leukemia

hematopoietic system
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
• increase in blast cell frequency after pIpC administration to induce Cre expression
• mice treated with polyinosine-polycytidine (pIpC) to induce Cre expression exhibit extramedullary hematopoiesis, with prominent expansion in the number of immature myeloid cells
• mice develop myeloproliferative disease shortly after pIpC administration to induce Cre expression with complete effacement of the splenic architecture
• reduction in bone marrow cellularity after pIpC administration to induce Cre expression
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression
• mice treated with pIpC to induce Cre expression exhibit an increase in hematopoietic stem cell proliferation but become depleted, most likely due to inhibition of self-renewal as no increase in cell death was observed
• mutants maintained on rapamycin after pIpC treatment do not exhibit expansion of hematopoietic stem cells

immune system
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression

tumorigenesis
• within 4-6 weeks after pIpC treatment, most mutants progress to leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia
• mutants maintained on rapamycin after pIpC treatment do not develop leukemia
• seen in mutants within 4-6 weeks after pIpC treatment
• seen in mutants within 4-6 weeks after pIpC treatment

endocrine/exocrine glands
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus




Genotype
MGI:5506907
cn12
Allelic
Composition
Pik3catm1Jjz/Pik3catm1Jjz
Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
Genetic
Background
FVB.Cg-Pik3catm1Jjz Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pik3catm1Jjz mutation (1 available); any Pik3ca mutation (33 available)
Pik3cbtm1Jjz mutation (1 available); any Pik3cb mutation (102 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(KRT14-cre)#Smr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
N
• mutants do not develop hamartomas over a period of 300 days and epidermal thickness is normal at 8 weeks of age




Genotype
MGI:5506905
cn13
Allelic
Composition
Pik3catm1Jjz/Pik3catm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
Genetic
Background
FVB.Cg-Pik3catm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pik3catm1Jjz mutation (1 available); any Pik3ca mutation (33 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(KRT14-cre)#Smr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• expanded basal cell layers
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants
• develop skin hamartomas with a median latency of 121 days

tumorigenesis
• develop skin hamartomas with a median latency of 121 days




Genotype
MGI:5506906
cn14
Allelic
Composition
Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
Genetic
Background
FVB.Cg-Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pik3cbtm1Jjz mutation (1 available); any Pik3cb mutation (102 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(KRT14-cre)#Smr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• accumulation of terminally differentiated suprabasal cells
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants
• develop skin hamartomas with a median latency of 131 days

tumorigenesis
• develop skin hamartomas with a median latency of 131 days




Genotype
MGI:5506904
cn15
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0
Genetic
Background
FVB.Cg-Ptentm1Hwu Tg(KRT14-cre)#Smr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(KRT14-cre)#Smr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• marker analysis indicates a perturbed basal-to-suprabasal transition
• expanded suprabasal layer as indicated by an increase in Keratin 10-postive cells
• increase in the number of epidermal cell layers at 8 weeks of age
• progressive development of multiple dermal lesions after weaning
• at 8 weeks of age
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis

tumorigenesis
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis




Genotype
MGI:5460854
cn16
Allelic
Composition
Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Calcatm1.1(cre/ERT2)Ptch mutation (0 available); any Calca mutation (11 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Rb1tm2Brn mutation (4 available); any Rb1 mutation (59 available)
Trp53tm1Brn mutation (6 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• all mice develop thyroid tumors

mortality/aging
• death within 3 months of tamoxifen treatment

respiratory system
• increased proliferation of pulmonary neuroendocrine cells
• small cell lung tumors 2.5 months after tamoxifen treatment

tumorigenesis
• all mice develop thyroid tumors
• small cell lung tumors 2.5 months after tamoxifen treatment
• increased invasiveness at 2.5 months after tamoxifen treatment




Genotype
MGI:4847601
cn17
Allelic
Composition
Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129 * 129S4/SvJae * BALB/c * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(cre/ERT)Nat mutation (1 available); any Gt(ROSA)26Sor mutation (317 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection

tumorigenesis
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
• 20% of males develop prostate cancer after 4OHT treatment
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

digestive/alimentary system
• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine

endocrine/exocrine glands
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
• 20% of males develop prostate cancer after 4OHT treatment
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts

reproductive system
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment
• 20% of males develop prostate cancer after 4OHT treatment
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment

integument
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

homeostasis/metabolism
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively




Genotype
MGI:5487550
cn18
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tgfbr1tm1.1Karl/Tgfbr1tm1.1Karl
Tg(KRT14-cre/ERT)20Efu/0
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tgfbr1tm1.1Karl mutation (0 available); any Tgfbr1 mutation (13 available)
Tg(KRT14-cre/ERT)20Efu mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Tgfbr1tm1.1Karl/Tgfbr1tm1.1Karl Ptentm1Hwu/Ptentm1Hwu Tg(KRT14-cre/ERT)20Efu/0 mice develop anal squamous cell carcinoma

tumorigenesis
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity (J:194652)
• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma (J:194652)
• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors (J:194652)
• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma (J:209026)
• invasion into adjacent muscle tissue is seen in some mice (J:209026)
• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines (J:209026)
• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction (J:209026)
• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma (J:209026)
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma
• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment

digestive/alimentary system
• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas




Genotype
MGI:4943513
cn19
Allelic
Composition
Hspa5tm1Alee/Hspa5tm1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hspa5tm1Alee mutation (0 available); any Hspa5 mutation (16 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
N
• mice do not develop detectable cancerous or precancerous lesions in the prostate




Genotype
MGI:4943514
cn20
Allelic
Composition
Hspa5tm1Alee/Hspa5+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hspa5tm1Alee mutation (0 available); any Hspa5 mutation (16 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane

reproductive system
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane

tumorigenesis
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane




Genotype
MGI:3805865
cn21
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
• mice develop prostate intraepithelial neoplasias

tumorigenesis
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
• mice develop prostate intraepithelial neoplasias

reproductive system
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks
• all mice develop invasive adenocarcinoma in all prostate lobes
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor
• mice develop prostate intraepithelial neoplasias




Genotype
MGI:4943512
cn22
Allelic
Composition
Hspa5tm1Alee/Hspa5tm1.1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hspa5tm1.1Alee mutation (1 available); any Hspa5 mutation (16 available)
Hspa5tm1Alee mutation (0 available); any Hspa5 mutation (16 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
N
• mice do not develop detectable cancerous or precancerous lesions in the prostate




Genotype
MGI:4882116
cn23
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(SFTPC-rtTA)5Jaw mutation (3 available)
Tg(tetO-cre)1Jaw mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
respiratory system
• doxycyline treated mice exhibit an increase in proliferation of epithelial cells lining conducting airways
• papillary epithelial hyperplasia is seen as early as 4-6 weeks of age in mice treated with doxycycline
• papillary epithelial hyperplasia is characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protrude into the airway lumens
• doxycyline treated mice exhibit an increase in proliferation of nonciliated bronchial and bronchiolar Clara cells
• mice treated with doxycycline exhibit bronchiolar epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
• mice treated with doxycycline exhibit bronchial epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells

endocrine/exocrine glands
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

nervous system
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

tumorigenesis
N
• overt pulmonary tumors are not observed in doxycycline treated mice at 6 weeks of age




Genotype
MGI:3813634
cn24
Allelic
Composition
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129 * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pgrtm2(cre)Lyd mutation (0 available); any Pgr mutation (24 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Trp53tm1Brn mutation (6 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• impaired survival is seen beginning around 2 months of age
• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells

reproductive system
• by P10, luminal and glandular epithelial hyperplasia are seen
• enlarged relative to conditional mutants that are wild type for Trp53
• hyperplasia progresses to carcinoma by 3 weeks of age

tumorigenesis
• hyperplasia progresses to carcinoma by 3 weeks of age

Mouse Models of Human Disease
OMIM ID Ref(s)
Endometrial Cancer 608089 J:139053




Genotype
MGI:5013951
cn25
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19+
Inpp5dtm1Rav/Inpp5dtm1Rav
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19tm1(cre)Cgn mutation (6 available); any Cd19 mutation (13 available)
Inpp5dtm1Rav mutation (0 available); any Inpp5d mutation (56 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• mutants exhibit a hunched posture by 4 months of age
• mutants exhibit lethargy by 4 months of age

growth/size/body
• mutants exhibit weight loss by 4 months of age

hematopoietic system
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
• mutants exhibit splenomegaly by 4 months of age
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
• B cells exhibit enhanced survival
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

immune system
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
• mutants exhibit splenomegaly by 4 months of age
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
• B cells exhibit enhanced survival
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

integument
• mutants exhibit ruffled fur by 4 months of age

mortality/aging
• severe morbidity and death occurs in all mutants by 1 year of age

tumorigenesis
• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma
• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma
• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney




Genotype
MGI:4836609
cn26
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Lyz2tm1(cre)Ifo/Lyz2+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lyz2tm1(cre)Ifo mutation (7 available); any Lyz2 mutation (11 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• macrophage recruitment to inflamed lungs is increased
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
• induction of neutropenia in mutants with the chemotherapeutic drug, cyclophosphamide, results in enhanced neutrophil accumulation in the lungs leading to better clearance of instilled bacteria and accelerated resolution of bacteria-induced lung inflammation
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
• mutants intratracheally infected with E.coli exhibit increased neutrophil recruitment to lungs and increased lung inflammation, pulmonary edema, and increased susceptibility to death compared to controls
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

hematopoietic system
• macrophage recruitment to inflamed lungs is increased
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice

homeostasis/metabolism
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines

mortality/aging
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

respiratory system
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls

cellular
• macrophage recruitment to inflamed lungs is increased




Genotype
MGI:4829791
cn27
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19tm1(cre)Cgn mutation (6 available); any Cd19 mutation (13 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
• expansion of the B1 cell population
• expansion of the MZ B cell compartment
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
• cultured B cells show increased apoptosis
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)
• decrease in IgG after TNP-OVA immunization
• increase in IgM after TNP-OVA immunization

immune system
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
• expansion of the B1 cell population
• expansion of the MZ B cell compartment
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
• cultured B cells show increased apoptosis
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)
• decrease in IgG after TNP-OVA immunization
• increase in IgM after TNP-OVA immunization

cellular
• cultured B cells show increased apoptosis




Genotype
MGI:4829792
cn28
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19tm1(cre)Cgn mutation (6 available); any Cd19 mutation (13 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• the population of B1 and MZ B cells that are absent in single homozygous CD19 mutants is restored
• mutants are capable of forming germinal centers when immunized with sheep red blood cells




Genotype
MGI:5543907
cn29
Allelic
Composition
Braftm1Mmcm/Braftm1Mmcm
Nkx3-1tm4(cre/ERT2)Mms/Nkx3-1+
Ptentm1Hwu/Pten+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Braftm1Mmcm mutation (2 available); any Braf mutation (27 available)
Nkx3-1tm4(cre/ERT2)Mms mutation (0 available); any Nkx3-1 mutation (10 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

endocrine/exocrine glands
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

mortality/aging
• mutants develop lethal prostate cancer 4 months after tamoxifen induction

tumorigenesis
• mutants develop lethal prostate cancer 4 months after tamoxifen induction
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction
• metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow

Mouse Models of Human Disease
OMIM ID Ref(s)
Prostate Cancer 176807 J:191327




Genotype
MGI:5704372
cn30
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Trp53tm2.1Tyj/Trp53+
Amhr2tm3(cre)Bhr/Amhr2+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (14 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Trp53tm2.1Tyj mutation (2 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• 70% of mice develop granulosa-cell tumors in the ovary
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube

endocrine/exocrine glands
• 70% of mice develop granulosa-cell tumors in the ovary
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube

tumorigenesis
• 70% of mice develop granulosa-cell tumors in the ovary
• 30% of mice develop high-grade serous carcinoma originating in the ovary
• however, mice do not develop serous carcinomas originating from the fallopian tube
• serous carcinoma spreads throughout the peritoneal cavity, to the omentum and across the peritoneal membrane, including the mesentery and diaphragm

mortality/aging
• median survival is 11.2 months of age, with mice dying between 7.6 and 15.3 months of age

homeostasis/metabolism

Mouse Models of Human Disease
OMIM ID Ref(s)
Ovarian Cancer 167000 J:222579




Genotype
MGI:5704363
cn31
Allelic
Composition
Dicer1tm1Tara/Dicer1tm1Tara
Ptentm1Hwu/Ptentm1Hwu
Amhr2tm3(cre)Bhr/Amhr2+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (14 available)
Dicer1tm1Tara mutation (1 available); any Dicer1 mutation (49 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube

tumorigenesis
• fallopian tube cancers subsequently spread to envelop the ovaries and then aggressively metastasize throughout the abdominal cavity, including the mesentery and pancreas, with prominent cancer lesions on the diaphragm and peritoneal membrane
• females develop early high-grade serous carcinomas in the fallopian tube
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube

mortality/aging
• after developing ascites, 100% of females die from the metastatic cancers between 6.5 and 13 months of age

reproductive system
• tumors are characterized by complex papillae and glands forming slit-like spaces nad solid sheets of tumor cells with pleomorphic nuclei, prominent nucleoli, and high mitotic activity, resembling high-grade human serous ovarian cancer
• origin of the serous carcinomas, however is the fallopian tube
• abnormal proliferation begins in the stromal compartment, not in the epithelial layer, of the fallopian tube; tumor cells in the stroma express epithelial markers indicating that stromal cells in the fallopian tube undergo a transition to an epithelial cell type during carcinoma formation

homeostasis/metabolism

Mouse Models of Human Disease
OMIM ID Ref(s)
Ovarian Cancer 167000 J:182161




Genotype
MGI:5704370
cn32
Allelic
Composition
Dicer1tm1Tara/Dicer1tm1Tara
Ptentm1Hwu/Ptentm1Hwu
Trp53tm2.1Tyj/Trp53+
Amhr2tm3(cre)Bhr/Amhr2+
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (14 available)
Dicer1tm1Tara mutation (1 available); any Dicer1 mutation (49 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Trp53tm2.1Tyj mutation (2 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

reproductive system
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

tumorigenesis
• mice show widespread peritoneal metastases, including omentum and diaphragm
• the overall metastatic tumor burden in fallopian tube-removed mice is less extensive than that of intact mice
• mice develop massive high-grade serous carcinomas that always arise from the fallopian tube
• however when fallopian tubes are removed, mice develop high-grade serous carcinomas originating from the ovary, indicating that the ovary can be a source of carcinomas but is less dominant in tumorigenesis than the fallopian tube
• ovary has on overgrowth of tumors composed of cells showing nuclear pleiomprhism, irregular chromatin distribution, macronucleoli, increased mitotic activity and widespread apoptosis resembling high-grade human serous ovarian cancer

mortality/aging
• premature death starting around 6 months of age with all mice dying by around 8 months of age
• fallopian tube-removed mice die at around 8-14 months of age after inducing ascites

homeostasis/metabolism

Mouse Models of Human Disease
OMIM ID Ref(s)
Ovarian Cancer 167000 J:222579




Genotype
MGI:5007685
cn33
Allelic
Composition
Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19tm1(cre)Cgn mutation (6 available); any Cd19 mutation (13 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(IghelMD4)4Ccg mutation (7 available)
Tg(ML5sHEL)5Ccg mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state
• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy
• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived




Genotype
MGI:4944270
cn34
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Rps6kb1tm1Gtho/Rps6kb1tm1Gtho
Tg(Mx1-cre)1Cgn/0
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Rps6kb1tm1Gtho mutation (0 available); any Rps6kb1 mutation (40 available)
Tg(Mx1-cre)1Cgn mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
• mice injected with pIpC to induce Pten deletion have an enlarged spleen

tumorigenesis
• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia, but at a slower rate than in single Pten mutants

mortality/aging
• mean survival time of mice injected with pIpC to induce Pten deletion is 46 days

immune system
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
• mice injected with pIpC to induce Pten deletion have an enlarged spleen

endocrine/exocrine glands
• mice injected with pIpC to induce Pten deletion have an enlarged thymus




Genotype
MGI:4838529
cn35
Allelic
Composition
Akt2tm1.1Mbb/Akt2tm1.1Mbb
Ptentm1Hwu/Ptentm1Hwu
Tg(Alb-cre)21Mgn/0
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Akt2tm1.1Mbb mutation (2 available); any Akt2 mutation (37 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Alb-cre)21Mgn mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• about 25-30% increase in fasting glucose levels at 1 month of age
• glucose intolerance

liver/biliary system
N
• the liver phenotype observed in single Pten mutants is significantly reduced, with liver weights, triglyceride levels in the liver and fatty liver almost similar to controls
• progenitor cell accumulation in the periductal region of livers occurs later than in single conditional Pten homozygotes, when injury conditions are already present
• mice do not show development of steatosis compared to single conditional Pten homozygotes

tumorigenesis
• mice exhibit a 6-month delay in liver tumor onset compared to conditional Pten homozygotes
• no mice develop liver tumors between 9 and 12 months of age and 25% of mice older than 12 months develop liver nodules
• however, treatment of 3 month old mice with 3,5-dietoxycarbonyl-1,4 dihydrocollidine (DDC) to induce liver injury leads to massive expansion of hepatic progenitors and development of premalignant lesions




Genotype
MGI:3844324
cn36
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Trp53tm1Brn mutation (6 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation

mortality/aging
• all mice treated with an adenovirus expressing cre die by 6 months of age

tumorigenesis
• urinary bladder tumors in Adeno-cre treated mice are of epithelial origins and exhibit features of carcinoma in situ and high-grade invasive carcinoma with areas of transitional cell, squamous, and sarcomatoid carcinoma
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation

Mouse Models of Human Disease
OMIM ID Ref(s)
Bladder Cancer 109800 J:146760




Genotype
MGI:4840094
cn37
Allelic
Composition
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(GFAP-cre)25Mes/0
Trp53tm1Tyj/Trp53+
Genetic
Background
involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nf1tm1Par mutation (4 available); any Nf1 mutation (75 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(GFAP-cre)25Mes mutation (2 available)
Trp53tm1Tyj mutation (9 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological
• exaggerated startle response
• ataxic gait
• generalized motor seizures

nervous system
• generalized motor seizures
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

tumorigenesis
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes




Genotype
MGI:4944273
cn38
Allelic
Composition
Errfi1tm1Jwj/Errfi1tm1Jwj
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Errfi1tm1Jwj mutation (0 available); any Errfi1 mutation (7 available)
Pgrtm2(cre)Lyd mutation (0 available); any Pgr mutation (24 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• survival time of double mutants is shorter than either single mutant, with mice dying by 16 weeks of age

reproductive system
• decrease in the number of apoptotic cells in the endothelium epithelium compared to single Pten mutants
• proliferation is increased in the endothelium epithelium
• mutants exhibit endometrial hyperplasia at 2 weeks of age and develop endometrial adenocarcinoma at 4 weeks of age
• however, myometrial hyperplasia is not observed in the uteri of mutants
• increase in uterine weight at 2 weeks of age, with weight at 4 weeks greater than in single Pten mutants
• development of endometrial cancer is accelerated compared to either single mutant

tumorigenesis
• development of endometrial cancer is accelerated compared to either single mutant
• mutants exhibit distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, colon and pancreas

Mouse Models of Human Disease
OMIM ID Ref(s)
Endometrial Cancer 608089 J:162027




Genotype
MGI:4836240
cn39
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-Bgeo/ALPP)1Lbe/0
Tg(Ela1-cre/ERT)1Dam/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(CAG-Bgeo/ALPP)1Lbe mutation (1 available)
Tg(Ela1-cre/ERT)1Dam mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
N
• 4 weeks after tamoxifen injections to induce Cre expression, pancreata exhibit no ductal metaplasia




Genotype
MGI:4836647
cn40
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Cnptm1(cre)Kan/Cnp+
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cnptm1(cre)Kan mutation (0 available); any Cnp mutation (10 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

digestive/alimentary system
• mutants develop megacolon later in life
• mutants develop hyperplasia of the salivary glands later in life

endocrine/exocrine glands
• mutants develop hyperplasia of the salivary glands later in life

nervous system
• increase in white matter volume
• progressive enlargement of all white matter tracts
• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray
• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age
• oligodendroglial hypertrophy is seen at 4 months of age
• increase in numbers of myelinating and nonmyelinating Schwann cells
• increase in myelin sheath thickness
• sciatic nerves are increased in size
• myelinated axons are more loosely spaced in sciatic nerves
• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons
• hypermyelination in both white and gray matter
• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure
• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated
• however, do not see ectopic myelination of CNS axons that normally are unmyelinated
• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin
• Remak Schwann cells also ensheath bundles of collagen fibrils
• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum

vision/eye
• mutants develop cataracts later in life

reproductive system
• poor breeding




Genotype
MGI:4839214
cn41
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Scgb1a1tm1.1(cre)Fjd mutation (0 available); any Scgb1a1 mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mice are viable and exhibit not visible abnormalities and remain healthy throughout 12 months of study, with normal lungs




Genotype
MGI:4839216
cn42
Allelic
Composition
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Krastm4Tyj mutation (4 available); any Kras mutation (32 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Scgb1a1tm1.1(cre)Fjd mutation (0 available); any Scgb1a1 mutation (17 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mean survival is 8 weeks

immune system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

respiratory system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma
• by 2 months of age, mutants exhibit tachypnea

tumorigenesis
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

growth/size/body
• by 2 months of age, mutants exhibit weight loss




Genotype
MGI:4944272
cn43
Allelic
Composition
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pgrtm2(cre)Lyd mutation (0 available); any Pgr mutation (24 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• proliferation is increased in the endothelium epithelium
• increase in uterine weight at 2 weeks of age
• mutants develop endometrial cancer
• mutants exhibit endometrial hyperplasia at 4 weeks of age and develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age

tumorigenesis
• mutants develop endometrial cancer
• mutants exhibit endometrial hyperplasia at 4 weeks of age and develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age




Genotype
MGI:4839561
cn44
Allelic
Composition
Ctnnb1tm2Kem/Ctnnb1tm2Kem
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctnnb1tm2Kem mutation (1 available); any Ctnnb1 mutation (26 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Cdh5-cre)7Mlia mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging




Genotype
MGI:4839562
cn45
Allelic
Composition
Ctnnb1tm2Kem/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctnnb1tm2Kem mutation (1 available); any Ctnnb1 mutation (26 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Cdh5-cre)7Mlia mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• die before P68 with vascular complications

hematopoietic system
• 100% of mutants develop myeloproliferative disorder at about P30

cardiovascular system
• mutants exhibit vascular complication




Genotype
MGI:4849443
cn46
Allelic
Composition
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nf1tm1Par mutation (4 available); any Nf1 mutation (75 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Gfap-cre)77.6Mvs mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
tumorigenesis
N
• mutants do not develop tumors




Genotype
MGI:3813633
cn47
Allelic
Composition
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pgrtm2(cre)Lyd mutation (0 available); any Pgr mutation (24 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• impaired survival is seen beginning around 5 months of age

reproductive system
• by P10, luminal and glandular epithelial hyperplasia are seen
• hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

tumorigenesis
• hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age

Mouse Models of Human Disease
OMIM ID Ref(s)
Endometrial Cancer 608089 J:139053




Genotype
MGI:5009703
cn48
Allelic
Composition
Artm1Verh/Y
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Artm1Verh mutation (1 available); any Ar mutation (17 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pbsn-cre)4Prb mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

endocrine/exocrine glands
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

tumorigenesis
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

Mouse Models of Human Disease
OMIM ID Ref(s)
Prostate Cancer 176807 J:172730




Genotype
MGI:4839510
cn49
Allelic
Composition
Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)7Mul/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Erbb2tm8(Erbb2)Mul mutation (0 available); any Erbb2 mutation (18 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(MMTV-cre)7Mul mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer

endocrine/exocrine glands
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer

tumorigenesis
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer

Mouse Models of Human Disease
OMIM ID Ref(s)
Breast Cancer 114480 J:133305




Genotype
MGI:4840096
cn50
Allelic
Composition
Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Trp53tm1Elee/Trp53+
Tg(GFAP-cre)25Mes/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nf1tm1Par mutation (4 available); any Nf1 mutation (75 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(GFAP-cre)25Mes mutation (2 available)
Trp53tm1Elee mutation (0 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological
• exaggerated startle response
• ataxic gait
• generalized motor seizures

nervous system
• generalized motor seizures
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

tumorigenesis
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci




Genotype
MGI:4839508
cn51
Allelic
Composition
Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Pten+
Tg(MMTV-cre)7Mul/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Erbb2tm8(Erbb2)Mul mutation (0 available); any Erbb2 mutation (18 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(MMTV-cre)7Mul mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
integument
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer

endocrine/exocrine glands
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer

tumorigenesis
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer
• 35% incidence of lung metastases compared with 5% in single Erbb2 mutants

Mouse Models of Human Disease
OMIM ID Ref(s)
Breast Cancer 114480 J:133305




Genotype
MGI:3783573
cn52
Allelic
Composition
Bcl2l11tm1.1Ast/Bcl2l11+
Ptentm1Hwu/Pten+
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bcl2l11tm1.1Ast mutation (2 available); any Bcl2l11 mutation (16 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(CD2-icre)4Kio mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice




Genotype
MGI:4836239
cn53
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0
Trp53tm1Tyj/Trp53tm1Tyj
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Pdx1-cre)89.1Dam mutation (0 available)
Trp53tm1Tyj mutation (9 available); any Trp53 mutation (147 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• 1 of 5 mutants develop a small acinar carcinoma
• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age

tumorigenesis
• 1 of 5 mutants develop a small acinar carcinoma
• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age




Genotype
MGI:4844100
cn54
Allelic
Composition
Cdkn1atm1Tyj/Cdkn1atm1Tyj
Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp1-cre)1Jig/0
Genetic
Background
involves: 129S2/SvPas * 129S4/SvJae * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Tyj mutation (3 available); any Cdkn1a mutation (46 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(Fabp1-cre)1Jig mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
• bladder urothelium exhibits increased cell proliferation

tumorigenesis




Genotype
MGI:4847591
cn55
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(CYP19A1-cre)1Jri/0
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(CYP19A1-cre)1Jri mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active
• after 3 months of age, ovaries contain increased numbers of corpora lutea
• females exhibit increased follicle growth
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries
• granulosa cells exhibit increased proliferation
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea

reproductive system
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active
• after 3 months of age, ovaries contain increased numbers of corpora lutea
• females exhibit increased follicle growth
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries
• granulosa cells exhibit increased proliferation
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea
• immature females primed with a superovulatory regiment of equine chorionic gonadotropin (eCG), followed by human CG, ovulate more oocytes than control mice, indicating advanced ovulation rate and increased ovulation
• females give birth to approximately 20% more pups than controls during a 6-month breeding period

tumorigenesis
N
• females do not develop ovarian tumors

cellular
• granulosa cells exhibit increased proliferation
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries
• the increased numbers of corpora lutea are at different stages of differentiation than in controls
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active




Genotype
MGI:5688693
cn56
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)#Tfln/0
Genetic
Background
involves: 129S4/SvJae
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (40 available)
Tg(MMTV-cre)#Tfln mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• mammary glands exhibit much larger lobules on the 13th day of pregnancy

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

endocrine/exocrine glands
• delay in the normal involution process and a decrease in cell apoptosis
• mammary glands exhibit much larger lobules on the 13th day of pregnancy
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age
• 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
• virgin glands contain many lobuloalveolar buds which are normally seen during pregnancy indicating an acceleration in lobuloalveolar-like precocious differentiation
• 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
• mammary glands after one pregnancy show intra-luminal focal cellular hyperplasia and dysplasia

integument
• delay in the normal involution process and a decrease in cell apoptosis
• mammary glands exhibit much larger lobules on the 13th day of pregnancy
• virgin mammary duct epithelium exhibits increased proliferation at 5 weeks and 14 weeks of age
• virgin mammary ducts develop excessive side branches or small protrusions at 6 weeks of age
• 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