Phenotypes associated with this allele

• Allele Symbol: Dicer1^tm1Tara
• Allele Name: targeted mutation 1, Alexander Tarakhovsky
• Allele ID: MGI:3622169
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Dicer1^tm1Tara/Dicer1^tm1Tara Tg(KRT14-cre)1Efu/0	involves: 129P2/OlaHsd	MGI:5319528
cn2	Dicer1^tm1Tara/Dicer1^tm1Tara Pten^tm1Hwu/Pten^tm1Hwu Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704363
cn3	Dicer1^tm1Tara/Dicer1^tm1Tara Pten^tm1Hwu/Pten^tm1Hwu Trp53^tm2Tyj/Trp53^+ Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704370
cn4	Dicer1^tm1Tara/Dicer1^tm1Tara Trp53^tm2Tyj/Trp53^+ Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd	MGI:5704374
cn5	Dicer1^tm1Tara/Dicer1^tm1Tara Amhr2^tm3(cre)Bhr/Amhr2^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5704375
cn6	Dicer1^tm1Tara/Dicer1^tm1Tara Foxn1^tm3(cre)Nrm/Foxn1^+	involves: 129P2/OlaHsd * C57BL/6NHsd	MGI:5312904
cn7	Dicer1^tm1Tara/Dicer1^tm1Tara Tg(KRT14-cre)1Efu/?	involves: 129P2/OlaHsd * CD-1	MGI:3625829

Genotype
MGI:5319528

cn1

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Tg(KRT14-cre)1Efu/0
• Genetic Background: involves: 129P2/OlaHsd

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

integument

epidermal cyst ( J:183622 )

• evaginating hair follicle cysts in the epidermis at P4

abnormal coat/ hair morphology ( J:201587 )

• less developed hair coat at P4.5

abnormal hair follicle morphology ( J:183622 )

• evaginating hair follicle cysts in the epidermis at P4

abnormal hair follicle development ( J:183622 , J:201587 )

• shortened and misangled hair follicle growth at P4 (J:183622)

• mice exhibit the loss of hair follicle stem cells in the bulge unlike in wild-type cells (J:201587)

abnormal skin appearance ( J:201587 )

• dehydrated at P4.5

abnormal skin physiology ( J:183622 )

• apoptotic cells in the basal epidermis

growth/size/body

epidermal cyst ( J:183622 )

• evaginating hair follicle cysts in the epidermis at P4

decreased body size ( J:201587 )

• at P4.5

Genotype
MGI:5704363

cn2

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Pten^tm1Hwu/Pten^tm1Hwu; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

increased metastatic potential ( J:182161 )

♀ • 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

increased carcinoma incidence ( J:182161 )

♀ • females develop early high-grade serous carcinomas in the fallopian tube

increased ovarian carcinoma incidence ( J:182161 )

♀ • 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

premature death ( J:182161 )

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

reproductive system

increased ovarian carcinoma incidence ( J:182161 )

♀ • 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 oviduct morphology ( J:182161 )

♀ • 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

ascites ( J:182161 )

♀

endocrine/exocrine glands

increased ovarian carcinoma incidence ( J:182161 )

♀ • 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:182161

Genotype
MGI:5704370

cn3

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Pten^tm1Hwu/Pten^tm1Hwu; Trp53^tm2Tyj/Trp53⁺; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

increased metastatic potential ( J:222579 )

♀ • 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

increased carcinoma incidence ( J:222579 )

♀ • 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

increased ovarian carcinoma incidence ( J:222579 )

♀ • 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 ( J:222579 )

♀ • 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

ascites ( J:222579 )

♀

endocrine/exocrine glands

increased ovarian carcinoma incidence ( J:222579 )

♀ • 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

increased ovarian carcinoma incidence ( J:222579 )

♀ • 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ovarian cancer		DOID:2394	OMIM:167000 OMIM:607893	J:222579

Genotype
MGI:5704374

cn4

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Trp53^tm2Tyj/Trp53⁺; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S7/SvEvBrd

neoplasm

neoplasm ( J:222579 )

♀N • mice do not develop ovarian or fallopian tube high grade serous carcinomas

Genotype
MGI:5704375

cn5

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Amhr2^tm3(cre)Bhr/Amhr2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

neoplasm

neoplasm ( J:222579 )

♀N • mice do not develop ovarian or fallopian tube high grade serous carcinomas

Genotype
MGI:5312904

cn6

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Foxn1^tm3(cre)Nrm/Foxn1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6NHsd

immune system

abnormal thymus morphology ( J:180783 )

• progressive disruption of thymic architecture, which is apparent by 1 week of age

• the thymus appears disorganized at 1 week of age

abnormal thymus epithelium morphology ( J:180783 )

• progressive loss of the epithelium

• by 3 weeks of age large epithelial voids are present in the cortex and the medullary epithelium is almost absent

• epithelial cells are skewed toward immature stages

abnormal thymus cortex morphology ( J:180783 )

• by 3 weeks large epithelial voids are present in the cortex

• thymocytes, macrophages and dense foci of CD19 + B cells are present in the epithelial voids

abnormal thymus medulla morphology ( J:180783 )

• by 3 weeks the medullary epithelium is almost absent

abnormal thymus physiology ( J:180783 )

• increased proliferation and apoptosis of the epithelium

abnormal thymus involution ( J:180783 )

• rapid premature involution with thymus size reduced by about 90% at 12 weeks of age

• castration does not eliminate premature involution

• unlike in wild-type mice, a low dose of poly I:C induces rapid involution

abnormal positive T cell selection ( J:180783 )

• at 3 weeks of age fewer CD3 + CD69 + CD4 + CD8 + double-positive thymocytes are present after positive selection

decreased CD4-positive, alpha-beta T cell number ( J:180783 )

• in the periphery at 3 weeks of age

decreased CD8-positive, alpha-beta T cell number ( J:180783 )

• in the periphery at 3 weeks of age

increased susceptibility to induced arthritis ( J:180783 )

• increased susceptibility (increased incidence) to collagen-induced arthritis but a lower severity of disease (reduced mean maximal disease score)

hematopoietic system

abnormal thymus morphology ( J:180783 )

• progressive disruption of thymic architecture, which is apparent by 1 week of age

• the thymus appears disorganized at 1 week of age

abnormal thymus epithelium morphology ( J:180783 )

• progressive loss of the epithelium

• by 3 weeks of age large epithelial voids are present in the cortex and the medullary epithelium is almost absent

• epithelial cells are skewed toward immature stages

abnormal thymus cortex morphology ( J:180783 )

• by 3 weeks large epithelial voids are present in the cortex

• thymocytes, macrophages and dense foci of CD19 + B cells are present in the epithelial voids

abnormal thymus medulla morphology ( J:180783 )

• by 3 weeks the medullary epithelium is almost absent

abnormal thymus physiology ( J:180783 )

• increased proliferation and apoptosis of the epithelium

abnormal thymus involution ( J:180783 )

• rapid premature involution with thymus size reduced by about 90% at 12 weeks of age

• castration does not eliminate premature involution

• unlike in wild-type mice, a low dose of poly I:C induces rapid involution

abnormal positive T cell selection ( J:180783 )

• at 3 weeks of age fewer CD3 + CD69 + CD4 + CD8 + double-positive thymocytes are present after positive selection

decreased CD4-positive, alpha-beta T cell number ( J:180783 )

• in the periphery at 3 weeks of age

decreased CD8-positive, alpha-beta T cell number ( J:180783 )

• in the periphery at 3 weeks of age

skeleton

increased susceptibility to induced arthritis ( J:180783 )

• increased susceptibility (increased incidence) to collagen-induced arthritis but a lower severity of disease (reduced mean maximal disease score)

endocrine/exocrine glands

abnormal thymus morphology ( J:180783 )

• progressive disruption of thymic architecture, which is apparent by 1 week of age

• the thymus appears disorganized at 1 week of age

abnormal thymus epithelium morphology ( J:180783 )

• progressive loss of the epithelium

• by 3 weeks of age large epithelial voids are present in the cortex and the medullary epithelium is almost absent

• epithelial cells are skewed toward immature stages

abnormal thymus cortex morphology ( J:180783 )

• by 3 weeks large epithelial voids are present in the cortex

• thymocytes, macrophages and dense foci of CD19 + B cells are present in the epithelial voids

abnormal thymus medulla morphology ( J:180783 )

• by 3 weeks the medullary epithelium is almost absent

abnormal thymus physiology ( J:180783 )

• increased proliferation and apoptosis of the epithelium

abnormal thymus involution ( J:180783 )

• rapid premature involution with thymus size reduced by about 90% at 12 weeks of age

• castration does not eliminate premature involution

• unlike in wild-type mice, a low dose of poly I:C induces rapid involution

Genotype
MGI:3625829

cn7

• Allelic Composition: Dicer1^tm1Tara/Dicer1^tm1Tara; Tg(KRT14-cre)1Efu/?
• Genetic Background: involves: 129P2/OlaHsd * CD-1

mortality/aging

postnatal lethality, complete penetrance ( J:106792 )

• began to lose weight within 1-2 day after birth, and died by day 6

• mutant mice are normal at birth and continued to feed for several days

homeostasis/metabolism

dehydration ( J:106792 )

• appeared dehydrated before death

cellular

increased apoptosis ( J:106792 )

• showed signs of apoptosis in skin as early as E17.5

• frequency of apoptosis was higher in the hair germ

• at P6.5, apoptosis is enriched in hair follicles, including abnormal cysts in the epidermis

integument

abnormal hair follicle morphology ( J:106792 )

• hair germs appear to evaginate into the epidermis

• hair germ-like cysts became prevalent, markedly distorting the overlying epidermis

abnormal vibrissa morphology ( J:106792 )

• showed malformed whiskers