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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Dicer1tm1Bdh
targeted mutation 1, Brian D Harfe
MGI:3589208
Summary 18 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Dicer1tm1Bdh/Dicer1tm1Bdh
Shhtm1(EGFP/cre)Cjt/Shh+
involves: 129 MGI:4943703
cn2
Amhr2tm3(cre)Bhr/Amhr2+
Dicer1tm1Bdh/Dicer1tm1Bdh
involves: 129 MGI:4360937
cn3
Dicer1tm1Bdh/Dicer1tm1Bdh
Hprttm1(Pck1-cre)Vhh/Y
involves: 129 * 129P2/OlaHsd MGI:5437747
cn4
Dicer1tm1Bdh/Dicer1+
Yy1tm2.1Yshi/Yy1+
Shhtm1(EGFP/cre)Cjt/Shh+
involves: 129 * 129S4/SvJae * C57BL/6 MGI:5902326
cn5
Dicer1tm1Bdh/Dicer1tm1Bdh
Nkx2-5tm1(cre)Rjs/Nkx2-5+
involves: 129 * 129S7/SvEvBrd * C57BL/6 MGI:5575766
cn6
Aicdatm1(cre)Njen/Aicda+
Dicer1tm1Bdh/Dicer1tm1Bdh
involves: 129 * C57BL/6 MGI:5315120
cn7
Dicer1tm1Bdh/Dicer1tm1Bdh
Edil3Tg(Sox2-cre)1Amc/Edil3+
involves: 129 * C57BL/6 * CBA MGI:6156399
cn8
Dicer1tm1Bdh/Dicer1tm1Bdh
H2az2Tg(Wnt1-cre)11Rth/0
involves: 129 * C57BL/6 * CBA/J MGI:4868120
cn9
Dicer1tm1Bdh/Dicer1+
H2az2Tg(Wnt1-cre)11Rth/0
involves: 129 * C57BL/6 * CBA/J MGI:4868201
cn10
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Cd4-cre)1Cwi/0
involves: 129 * C57BL/6 * DBA/2 MGI:3806246
cn11
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Prrx1-cre)1Cjt/0
involves: 129 * C57BL/6J * SJL/J MGI:3589871
cn12
Dicer1tm1Bdh/Dicer1tm1Bdh
Sox1tm1(cre)Take/Sox1+
involves: 129 * C57BL/6NCrlj * CBA/JNCrlj MGI:6156401
cn13
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Foxp3-EGFP/icre)1aJbs/0
involves: 129 * NOD/ShiLt MGI:3809798
cn14
Dicer1tm1Bdh/Dicer1tm1Bdh
Foxp3tm4(YFP/icre)Ayr/Y
involves: 129S1/Sv * 129X1/SvJ MGI:3806255
cn15
Dicer1tm1Bdh/Dicer1tm1Bdh
Foxp3tm4(YFP/icre)Ayr/Foxp3tm4(YFP/icre)Ayr
involves: 129S1/Sv * 129X1/SvJ MGI:3806256
cn16
Aicdatm1(cre)Njen/Aicda+
Bcl2l11tm1Ast/Bcl2l11tm1Ast
Dicer1tm1Bdh/Dicer1tm1Bdh
involves: 129S1/Sv * C57BL/6 MGI:5315121
cn17
Defb41tm1(icre)Psip/Defb41+
Dicer1tm1Bdh/Dicer1tm1Bdh
involves: 129S6/SvEvTac * C57BL/6N MGI:5439018
cn18
Dicer1tm1Bdh/Dicer1tm1Bdh
Plekha5Tg(AMH-cre)1Flor/0
involves: 129/Sv * C57BL/6 * SJL MGI:4360936


Genotype
MGI:4943703
cn1
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Shhtm1(EGFP/cre)Cjt/Shh+
Genetic
Background
involves: 129
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Shhtm1(EGFP/cre)Cjt mutation (1 available); any Shh mutation (23 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

respiratory system
• at E12.5, fewer branches are observed and the distal tips of the newly formed branches appear dilated
• the number of dilated branching tips observed at E12.5 corresponds to the number of large, fluid-filled sacs seen at E15.5
• defective branching morphogenesis occurs prior to the increased cell death seen in the distal epithelium at E13.0
• at E11.75, expression of Fgf10 (a key gene involved in lung development) is already up-regulated and expanded in the mesenchyme of mutant lungs
• at E15.5, mutant lung epithelial cells form large, fluid-filled sacs within each lobe, indicating a severe branching defect
• at E15.5, the mutant epithelium is often detached from the mesenchyme, unlike in control lungs
• at E12.25, increased epithelial cell death is ectopically observed in the secondary bronchi of mutant lungs in addition to the normal pattern of cell death seen in the trachea and primary bronchi
• at E12.5 and E12.75, intense epithelial cell death is prolonged in the mutant trachea and bronchi, unlike in control and wild type lungs
• by E13.0, aberrant cell death is observed in the entire mutant lung epithelium, including the distal branching region, but not in the mesenchyme
• after E13.5, each mutant lung lobe is proportionally smaller than that in control lungs
• however, each lobe maintains a normal shape, indicating a normal lobation pattern




Genotype
MGI:4360937
cn2
Allelic
Composition
Amhr2tm3(cre)Bhr/Amhr2+
Dicer1tm1Bdh/Dicer1tm1Bdh
Genetic
Background
involves: 129
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Amhr2tm3(cre)Bhr mutation (1 available); any Amhr2 mutation (22 available)
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• mutant females display normal estrous cycles and mating behavior relative to control littermates
• adult day-1 pregnant female mutants display reduced ovarian weights relative to age-matched control littermates
• unlike wild-type, mutant oviducts lack extensive coiling and appear more transparent under a dissecting microscope
• distended sac-like structures filled with clear fluid are observed at the end of the oviduct near the uterotubal junction
• oviducts of both immature and pregnant female mutants rupture easily, do not appear patent, and cannot be flushed
• mutant oviducts display a disorganized epithelial cell layer while the isthmus region is almost devoid of smooth muscle tissue
• both untreated and eCG+hCG-treated immature (day 25) and adult day-1 pregnant female mutants display shorter oviducts that are less than one half the length of control littermates
• mutant uteri appear more transparent than control uteri under a dissecting microscope
• both eCG+hCG-treated immature and adult pregnant female mutants exhibit reduced numbers of uterine glands relative to control littermates
• both eCG+hCG-treated immature and adult pregnant female mutants display a thinner myometrial layer relative to control littermates
• both untreated and eCG+hCG-treated immature (day 25) female mutants show a significant reduction in the length and diameter of uterine horns relative to control littermates
• mutant uteri are hypotrophic, approximately two thirds the length of control littermates, and contain much less smooth muscle
• adult day-1 pregnant female mutants display reduced uterine weights relative to age-matched control littermates
• unlike embryos developing in wild-type females, embryos in mutant females fail to enter the uterus on day 4 of pregnancy, indicating disruption of oviductal transport; most are found in the upper one third of the oviduct instead of the uterus
• only a few embryos progress through the oviduct to the isthmus; however, these are mostly fragmented and some zonae pellucidae are lost
• in contrast, in vitro cultured pronuclear (day-1) embryos collected from mutant donors develop at a similar rate as those derived from wild-type females
• immature eCG+hCG-treated female mutants display a reduced ovulation rate relative to similarly treated wild-type females
• immature mutant females given eCG alone (46 hrs) exhibit fewer large antral follicles in their ovaries than similarly treated control littermates
• female mutants exhibit decreased numbers of naturally ovulated cumulus-oocyte complexes relative to control littermates
• embryos collected from mutant females on day-3 of pregnancy appear developmentally delayed relative to control embryos
• embryos collected from mutant females on day-4 of pregnancy exhibit increased fragmentation and degeneration relative to control embryos
• however, in vitro fertilized oocytes derived from mutant donor mice are able to establish a pregnancy in wild-type recipients with normal fetal development up to at least E15
• at day-6 and -7 of pregnancy, mutant females exhibit no evidence of implantation; in contrast, all wild-type females display 9.8 0.4 implantation sites per dam
• mutant females fail to produce any offspring over a 5-month breeding period with adult wild-type males of known fertility
• in contrast, male mutants are able to sire multiple litters with wild-type females

homeostasis/metabolism
N
• eCG+hCG-treated immature female mutants show no significant changes in estrogen levels relative to control littermates
• on day-6 of pregnancy, mutant females show a slight (24%) decrease in serum progesterone levels relative to controls
• however, no significant changes in serum progesterone concentrations are noted through day-4 of pregnancy

endocrine/exocrine glands
• both eCG+hCG-treated immature and adult pregnant female mutants exhibit reduced numbers of uterine glands relative to control littermates
• adult day-1 pregnant female mutants display reduced ovarian weights relative to age-matched control littermates




Genotype
MGI:5437747
cn3
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Hprttm1(Pck1-cre)Vhh/Y
Genetic
Background
involves: 129 * 129P2/OlaHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Hprttm1(Pck1-cre)Vhh mutation (0 available); any Hprt mutation (30 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
renal/urinary system
N
• mice exhibit normal kidney size, renal histology, and renal function throughout a 6-month observation period
• at 8-10 weeks of age, BUN levels and serum creatinine levels are normal relative to those in wild-type controls
• following bilateral kidney ischemia/reperfusion injury, mice exhibit decreased creatinine plasma levels, significantly less cortical and outer medulla tubular damage, lower tubular apoptosis, and improved survival relative to wild-type controls

homeostasis/metabolism
• following bilateral kidney ischemia/reperfusion injury, mice exhibit decreased creatinine plasma levels, significantly less cortical and outer medulla tubular damage, lower tubular apoptosis, and improved survival relative to wild-type controls




Genotype
MGI:5902326
cn4
Allelic
Composition
Dicer1tm1Bdh/Dicer1+
Yy1tm2.1Yshi/Yy1+
Shhtm1(EGFP/cre)Cjt/Shh+
Genetic
Background
involves: 129 * 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Shhtm1(EGFP/cre)Cjt mutation (1 available); any Shh mutation (23 available)
Yy1tm2.1Yshi mutation (0 available); any Yy1 mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
respiratory system
N
• embryos do not present lung defects




Genotype
MGI:5575766
cn5
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Nkx2-5tm1(cre)Rjs/Nkx2-5+
Genetic
Background
involves: 129 * 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Nkx2-5tm1(cre)Rjs mutation (1 available); any Nkx2-5 mutation (14 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
muscle

mortality/aging

cardiovascular system
• by E12.5
• embryos die at E12.5 from cardiac failure

homeostasis/metabolism
• by E12.5




Genotype
MGI:5315120
cn6
Allelic
Composition
Aicdatm1(cre)Njen/Aicda+
Dicer1tm1Bdh/Dicer1tm1Bdh
Genetic
Background
involves: 129 * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1(cre)Njen mutation (0 available); any Aicda mutation (41 available)
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• before immunization, mice have normal B-cell subsets in the bone marrow, spleen, lymph nodes, and peritoneal cavities
• significantly decreased numbers (6- to 10 fold) of germinal center (GC) B cells are present in the spleen at day 10 after immunization
• drastic reductions in GC B cell populations in Peyer patches and mesenteric lymph nodes are also observed
• NP-specific memory B (IgG1) cells are essentially absent from spleens of mice 56 days after primary immunization with NP-CGG
• NP-specific IgG1 antibody-secreting cells (ASCs) are absent from the bone marrow at 56 days after primary immunization with NP-CGG
• at 10 days after immunization, numbers of proliferating GC B cells are 3- to 5-fold lower than in wild-type, suggesting impaired proliferative capacity
• GC B cells are mores susceptible to cell death; numbers of apoptotic cells are 30 to 50% higher than in controls at day 10 after immunization
• upon immunization with a T cell dependent antigen (NP-CGG), mice display normal levels of NP-specific IgM antibodies at 14, 21, and 28 days following exposure, while NP-specific IgG1, IgGb and IgG3 antibody titers are drastically reduced
• mice have lower basal serum levels of IgG1, IgG2b, IgG3, and IgA compared to wild-type
• IgM level is normal

hematopoietic system
• significantly decreased numbers (6- to 10 fold) of germinal center (GC) B cells are present in the spleen at day 10 after immunization
• drastic reductions in GC B cell populations in Peyer patches and mesenteric lymph nodes are also observed
• NP-specific memory B (IgG1) cells are essentially absent from spleens of mice 56 days after primary immunization with NP-CGG
• NP-specific IgG1 antibody-secreting cells (ASCs) are absent from the bone marrow at 56 days after primary immunization with NP-CGG
• at 10 days after immunization, numbers of proliferating GC B cells are 3- to 5-fold lower than in wild-type, suggesting impaired proliferative capacity
• GC B cells are mores susceptible to cell death; numbers of apoptotic cells are 30 to 50% higher than in controls at day 10 after immunization
• mice have lower basal serum levels of IgG1, IgG2b, IgG3, and IgA compared to wild-type
• IgM level is normal




Genotype
MGI:6156399
cn7
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Edil3Tg(Sox2-cre)1Amc/Edil3+
Genetic
Background
involves: 129 * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Edil3Tg(Sox2-cre)1Amc mutation (4 available); any Edil3 mutation (6 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
embryo
• observed at E8.5

nervous system
• observed at E8.5




Genotype
MGI:4868120
cn8
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
H2az2Tg(Wnt1-cre)11Rth/0
Genetic
Background
involves: 129 * C57BL/6 * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
H2az2Tg(Wnt1-cre)11Rth mutation (2 available); any H2az2 mutation (20 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

cardiovascular system
• discontinuance of the ascending aortic arch with the descending aorta, indicating improper pattering of the aortic arch due to a left fourth aortic arch defect
• the outflow tract does not fully septate into a pulmonary artery and aorta in some cases, resulting in the persistence of a common outflow vessel

craniofacial
• severe craniofacial defects are seen by E14.5
• although pharyngeal arches appear similar to wild-type in emergence, size and shape, expression of Dlx2 and Fgf8 are downregulated in pharyngeal arch 1
• apoptosis is increased in the first pharyngeal arch at E11.5

embryo
• although pharyngeal arches appear similar to wild-type in emergence, size and shape, expression of Dlx2 and Fgf8 are downregulated in pharyngeal arch 1
• apoptosis is increased in the first pharyngeal arch at E11.5

hematopoietic system
• thymus development is absent

immune system
• thymus development is absent

nervous system
• loss of neural crest cell derived neuronal tissue from the thoracic sympathetic ganglia
• loss of neural crest cell derived neuronal tissue from the dorsal root ganglia

skeleton
• neural crest cell derived maxillary and mandibular regions of the face and frontonasal process lack cartilaginous tissue, however mesodermally derived cartilage near the base of the skull is present

endocrine/exocrine glands
• thymus development is absent

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
DiGeorge syndrome DOID:11198 OMIM:188400
J:166758




Genotype
MGI:4868201
cn9
Allelic
Composition
Dicer1tm1Bdh/Dicer1+
H2az2Tg(Wnt1-cre)11Rth/0
Genetic
Background
involves: 129 * C57BL/6 * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
H2az2Tg(Wnt1-cre)11Rth mutation (2 available); any H2az2 mutation (20 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type

immune system
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type

endocrine/exocrine glands
• thymus development is delayed at E14.5, but by E16.5, the thymus is indistinguishable from wild-type




Genotype
MGI:3806246
cn10
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Cd4-cre)1Cwi/0
Genetic
Background
involves: 129 * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Tg(Cd4-cre)1Cwi mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• mature peripheral T reg cells are reduced in frequency

immune system
• mature peripheral T reg cells are reduced in frequency




Genotype
MGI:3589871
cn11
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Prrx1-cre)1Cjt/0
Genetic
Background
involves: 129 * C57BL/6J * SJL/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Tg(Prrx1-cre)1Cjt mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
limbs/digits/tail
• forelimbs show loss of digits and some fusion of digits
• at E11 the forelimbs are smaller and at E12.5 the forelimb size resembles that of wild-type forelimbs at E11.5
• starting at E10.5 increased cell death is seen in the limb mesoderm
• the hindlimbs are smaller but not as severely affected as the forelimbs
• starting at E12.5 increased cell death is seen in the limb mesoderm

skeleton
• the long bones of the arms and legs appear twisted
• bone formation from cartilage is delayed in the long bones of the limbs




Genotype
MGI:6156401
cn12
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Sox1tm1(cre)Take/Sox1+
Genetic
Background
involves: 129 * C57BL/6NCrlj * CBA/JNCrlj
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Sox1tm1(cre)Take mutation (1 available); any Sox1 mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

embryo




Genotype
MGI:3809798
cn13
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Tg(Foxp3-EGFP/icre)1aJbs/0
Genetic
Background
involves: 129 * NOD/ShiLt
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Tg(Foxp3-EGFP/icre)1aJbs mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• all mice die by 6-8 weeks of age

growth/size/body
• aging animals display weight loss

behavior/neurological
• aging animals display reduced mobility

immune system
• number of CTLA4-expressing CD4+ Foxp3- effector T cells increase to >50% of splenic and >70% of lymph node CD4+ T cells compared to <10% in wild-type littermates
• T reg cells have a higher percentage of CD103+ T cells and greater number of CD62lo cells
• percentage of regulatory T (T reg) cells in spleen and peripheral blood is reduced to 33% of controls
• observed in all aging animals (>5 weeks of age)
• dramatic increase in splenic T cells is seen in 4-6 week old mice relative to controls
• many effector T cells have high levels of Il4, Il10 and interferon gamma, Ifng whereas <1% of cells from wild-type express Il4, Il10, Il17 or Ifng
• CD4+ Foxp3+ T regs have a more prominent activated phenotype (increased expression of CD25, CTLA4 and glucocorticoid-induced TNFR)
• dramatic increase in lymph node T cells is seen in 4-6 week old mice; however percentage of regulatory T cells is maintained
• observed in all aging animals (>5 weeks of age)
• tissue displays extensive mononuclear cell infiltration
• tissue displays extensive mononuclear cell infiltration
• tissue has dense predominantly peribronchovascular infiltrates, composed of CD4+ and Cd8+ T cells

hematopoietic system
• number of CTLA4-expressing CD4+ Foxp3- effector T cells increase to >50% of splenic and >70% of lymph node CD4+ T cells compared to <10% in wild-type littermates
• T reg cells have a higher percentage of CD103+ T cells and greater number of CD62lo cells
• percentage of regulatory T (T reg) cells in spleen and peripheral blood is reduced to 33% of controls
• observed in all aging animals (>5 weeks of age)
• dramatic increase in splenic T cells is seen in 4-6 week old mice relative to controls
• many effector T cells have high levels of Il4, Il10 and interferon gamma, Ifng whereas <1% of cells from wild-type express Il4, Il10, Il17 or Ifng
• CD4+ Foxp3+ T regs have a more prominent activated phenotype (increased expression of CD25, CTLA4 and glucocorticoid-induced TNFR)

liver/biliary system
• tissue displays extensive mononuclear cell infiltration

respiratory system
• tissue displays extensive mononuclear cell infiltration
• tissue has dense predominantly peribronchovascular infiltrates, composed of CD4+ and Cd8+ T cells

skeleton
• seen in aging animals




Genotype
MGI:3806255
cn14
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Foxp3tm4(YFP/icre)Ayr/Y
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Foxp3tm4(YFP/icre)Ayr mutation (2 available); any Foxp3 mutation (42 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• females become ill at 2-3 weeks, exhibiting 100% mortality at <25 days

immune system
• cuffing around blood vessels by inflammatory cells in pancreas, kidney and skeletal muscle is observed
• large areas are infiltrated by inflammatory cells in moribund mice
• large areas are infiltrated by inflammatory cells in moribund mice

hematopoietic system

cardiovascular system
• cuffing around blood vessels by inflammatory cells in pancreas, kidney and skeletal muscle is observed

liver/biliary system
• large areas are infiltrated by inflammatory cells in moribund mice

respiratory system
• large areas are infiltrated by inflammatory cells in moribund mice




Genotype
MGI:3806256
cn15
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Foxp3tm4(YFP/icre)Ayr/Foxp3tm4(YFP/icre)Ayr
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Foxp3tm4(YFP/icre)Ayr mutation (2 available); any Foxp3 mutation (42 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• males become ill at 2-3 weeks, exhibiting 100% mortality at <25 days

immune system
• cuffing around blood vessels by inflammatory cells in pancreas, kidney and skeletal muscle is observed
• large areas are infiltrated by inflammatory cells in moribund mice
• large areas are infiltrated by inflammatory cells in moribund mice

hematopoietic system

cardiovascular system
• cuffing around blood vessels by inflammatory cells in pancreas, kidney and skeletal muscle is observed

liver/biliary system
• large areas are infiltrated by inflammatory cells in moribund mice

respiratory system
• large areas are infiltrated by inflammatory cells in moribund mice




Genotype
MGI:5315121
cn16
Allelic
Composition
Aicdatm1(cre)Njen/Aicda+
Bcl2l11tm1Ast/Bcl2l11tm1Ast
Dicer1tm1Bdh/Dicer1tm1Bdh
Genetic
Background
involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aicdatm1(cre)Njen mutation (0 available); any Aicda mutation (41 available)
Bcl2l11tm1Ast mutation (0 available); any Bcl2l11 mutation (15 available)
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• rescued germinal center B cells cannot effectively differentiate into antibody-secreting cells (AScs), and fail to differentiate into high affinity ASCs
• numbers are reduced in spleen relative to wild-type, but are dramatically increased on a Bcl2l11-deficient background compared to conditional knockouts with wild-type background
• NP-specific IgG1 antibody-secreting cells (ASCs) are present only at 20-25% of the numbers observed in wild-type spleens at day 12 after immunization
• high affinity ASCs are almost undetectable and bone marrow

hematopoietic system
• rescued germinal center B cells cannot effectively differentiate into antibody-secreting cells (AScs), and fail to differentiate into high affinity ASCs
• numbers are reduced in spleen relative to wild-type, but are dramatically increased on a Bcl2l11-deficient background compared to conditional knockouts with wild-type background
• NP-specific IgG1 antibody-secreting cells (ASCs) are present only at 20-25% of the numbers observed in wild-type spleens at day 12 after immunization
• high affinity ASCs are almost undetectable and bone marrow




Genotype
MGI:5439018
cn17
Allelic
Composition
Defb41tm1(icre)Psip/Defb41+
Dicer1tm1Bdh/Dicer1tm1Bdh
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Defb41tm1(icre)Psip mutation (0 available); any Defb41 mutation (3 available)
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• sperm number is reduced in mutant epididymides; at 6 months, number of tubular cross sections without sperm is increased due to obstruction of efferent ducts; however, number of sperm with angulated tails is not increased at 2 months compared to controls

reproductive system
• sperm number is reduced in mutant epididymides; at 6 months, number of tubular cross sections without sperm is increased due to obstruction of efferent ducts; however, number of sperm with angulated tails is not increased at 2 months compared to controls
• efferent ducts are enlarged at 2 months
• disruption of epithelium resulting from fluid back-pressure is noted in 6-month old mice
• mutant males have a thicker smooth muscle layer than controls at 2 months, showing 3 muscle cell layers surrounding epididymal duct compared to one in controls
• initial segment (IS) of epididymis is much smaller than in controls and cannot be distinguished from the caput epididymis (CAP) whereas in controls the IS is readily discerned due to endogenous beta-gal activity
• epithelial cell layer is disorganized in mutants at 2 months with greater disturbance observed in 6-month old males
• numbers of apoptotic cells are higher in the IS and CAP of mutants relative to controls
• height of epithelium in initial segment of mutants is reduced below that of control animals; epithelial cell height in IS of mutants is significantly lower than in controls
• epithelial cells of IS in 45 day-old animals show regression to an undifferentiated state similar to that observed at 14 days
• despite increased cell proliferation, epididymides of mutants are significantly smaller than control (by weight at 2 months, but at 6 months there is no significant difference in epididymides weights)
• 2-3 month-old males fail to produce offspring when mated to wild-type females, even though sperm is detected in the cauda epididymides
• increased cell proliferation is observed in the proximal epididymides of 2 month-old mice based on Ki-67 staining (about 2-fold higher in the initial segment (IS) and 6-fold higher in the caput region (CAP) in mutants vs. control)

endocrine/exocrine glands
• efferent ducts are enlarged at 2 months
• disruption of epithelium resulting from fluid back-pressure is noted in 6-month old mice




Genotype
MGI:4360936
cn18
Allelic
Composition
Dicer1tm1Bdh/Dicer1tm1Bdh
Plekha5Tg(AMH-cre)1Flor/0
Genetic
Background
involves: 129/Sv * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dicer1tm1Bdh mutation (4 available); any Dicer1 mutation (61 available)
Plekha5Tg(AMH-cre)1Flor mutation (1 available); any Plekha5 mutation (27 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• adult males show no differences in mounting and copulatory activity or in testicular descent and masculinization of internal reproductive organs (seminal vesicles and prostate) relative to control littermates
• at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts
• at P60, mutant male germ cells are severely disorganized and reduced in number
• by 6 months of age, the few remaining tubes are almost completely devoid of germ cells
• at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts
• significant male germ cell apoptosis is noted at P15 and P21
• by P42, mutant male germ cells exhibit extensive apoptosis
• Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age
• however, no significant differences in testicular testosterone levels are observed from P0 to P60
• at P60, the mutant seminiferous epithelium appears disorganized
• as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen
• at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
• significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells
• by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed
• as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery
• at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen
• as early as P5, numerous pycnotic cells are detected within mutant tubes
• at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen
• by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology
• at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes
• by 6 months of age, mutant testis size is only 5% of that in control littermates
• at P60, mutant males show a 90% reduction in testis weight relative to control littermates
• severe testicular degeneration is noted at P60 and worsens upon aging
• by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes
• at P60, mutant males show severe spermatogenic defects including vacuolization, Sertoli-cell-only tubes, tubes with spermatogenic arrest at an early post-meiotic stage, and disorganization of the seminiferous epithelium
• at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes
• mutant males fail to produce any offspring during a 6-month mating period with wild-type C57BL/6J females

endocrine/exocrine glands
• Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age
• however, no significant differences in testicular testosterone levels are observed from P0 to P60
• at P60, the mutant seminiferous epithelium appears disorganized
• as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen
• at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
• significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells
• by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed
• as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery
• at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen
• as early as P5, numerous pycnotic cells are detected within mutant tubes
• at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen
• by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology
• at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes
• by 6 months of age, mutant testis size is only 5% of that in control littermates
• at P60, mutant males show a 90% reduction in testis weight relative to control littermates
• severe testicular degeneration is noted at P60 and worsens upon aging
• by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes

cellular
• at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts
• at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes
• at P60, mutant male germ cells are severely disorganized and reduced in number
• by 6 months of age, the few remaining tubes are almost completely devoid of germ cells
• at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts
• significant male germ cell apoptosis is noted at P15 and P21
• by P42, mutant male germ cells exhibit extensive apoptosis





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last database update
10/08/2019
MGI 6.14
The Jackson Laboratory