Tg(MMTVtTA)1Mam Transgene Detail MGI Mouse (MGI:3053958)

Tg(MMTVtTA)1Mam
Transgene Detail

Nomenclature

Symbol:	Tg(MMTVtTA)1Mam
Name:	transgene insertion 1, Lothar Hennighausen
MGI ID:	MGI:3053958
Synonyms:	MMTV-tTA
Transgene:	Tg(MMTVtTA)1Mam Location: unknown

Transgene
origin

Strain of Origin:

C57BL/6 and SJL

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The MMTV LTR was used to target expression of tetracycline-controlled transactivator protein (tTA) to the epithelial cells of secretory organs and skin. The tetracycline resistance gene (TetR) was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). (J:92586)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1	tg2	tg3	tg4	tg5
behavior/neurological		√
lethargy		√
		tg1	tg2	tg3	tg4	tg5
cellular				√	√
increased apoptosis				√	√
		tg1	tg2	tg3	tg4	tg5
endocrine/exocrine glands			√			√
abnormal gland morphology						√
abnormal sebaceous gland morphology			√			√
abnormal meibomian gland morphology			√
absent meibomian glands						√
abnormal preputial gland morphology						√
enlarged sebaceous gland						√
		tg1	tg2	tg3	tg4	tg5
growth/size						√
decreased body weight						√
		tg1	tg2	tg3	tg4	tg5
hematopoietic system		√		√	√
enlarged spleen		√		√	√
anemia				√	√
increased leukocyte cell number				√	√
decreased platelet cell number				√	√
		tg1	tg2	tg3	tg4	tg5
immune system		√		√	√	N
immune system phenotype						N
enlarged spleen		√		√	√
increased leukocyte cell number				√	√
enlarged lymph nodes				√	√
		tg1	tg2	tg3	tg4	tg5
life span/aging		√		√	√
premature death		√		√	√
		tg1	tg2	tg3	tg4	tg5
limbs/digits/tail			N
limbs/digits/tail phenotype			N
		tg1	tg2	tg3	tg4	tg5
renal/urinary system						√
abnormal preputial gland morphology						√
		tg1	tg2	tg3	tg4	tg5
reproductive system						√
abnormal preputial gland morphology						√
		tg1	tg2	tg3	tg4	tg5
skeleton				√	√
abnormal bone marrow morphology				√	√
		tg1	tg2	tg3	tg4	tg5
skin/coat/nails			√			√
skin/coat/nails phenotype			N
abnormal coat/ hair morphology						√
disheveled coat						√
abnormal hair growth						√
short hair						√
abnormal hair types						√
abnormal guard hair			√
decreased zigzag hair amount			√
absent zigzag hairs						√
abnormal skin morphology						√
		tg1	tg2	tg3	tg4	tg5
tumorigenesis		√		√	√
leukemia		√		√	√
B cell derived lymphoma		√
		tg1	tg2	tg3	tg4	tg5
vision/eye			√			√
abnormal eyelid morphology			√
abnormal meibomian gland morphology			√
absent meibomian glands						√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Dnmt1^tm1Sjk/Dnmt1⁺ Tg(IghMyc)22Bri/0 Tg(MMTVtTA)1Mam/0	involves: 129S4/SvJae * C57BL/6
life span/aging premature death (J:93549) without doxycycline treatment median survival is 82 days, with doxycycline treatment the improves to 145 days tumorigenesis leukemia (J:93549) in the absence of doxycycline, lymphoblastic leukemia is seen by 2 weeks of age in 5 - 7 week old triple transgenics with lymphoblastic leukemia doxycycline treatment resulted in normalization of the WBC count and restoration of normal hematopoiesis B cell derived lymphoma (J:93549) bulky B cell derived lymphomas, similar to those in Tg(IghMyc)22Bri single transgenics, are seen in older triple transgenics after treatment with doxycycline behavior/neurological lethargy (J:93549) transgenics with leukemia are lethargic, doxycycline treatment returns activity levels to normal hematopoietic system enlarged spleen (J:93549) in the absence of doxycycline, mutants develop an enlarged spleen with doxycycline treatment the spleen returns to its normal size immune system enlarged spleen (J:93549) in the absence of doxycycline, mutants develop an enlarged spleen with doxycycline treatment the spleen returns to its normal size
Genotype	Allelic Composition	Genetic Background
tg2	Tg(MMTVtTA)1Mam/0 Tg(tetO-Eda*A1)1Dsch/0	involves: C57BL/6
endocrine/exocrine glands abnormal sebaceous gland morphology (J:99510) hypertrophy of sebaceous glands associated with hair follicles of the eyelids abnormal meibomian gland morphology (J:86628) enlarged meibomian gland in the absence of doxicycline (transgene is expressed) however, the preputial gland and sweat glands are normal skin/coat/nails skin/coat/nails phenotype (J:86628) in the absence of doxicycline (the transgene is expressed), overall skin morphology is indistinguishable from controls abnormal guard hair (J:86628) in the absence of doxicycline (the transgene is expressed), guard hair numbers are somewhat increased to 8.7% compared to 5-6% in wild-type decreased zigzag hair amount (J:86628) in the absence of doxicycline), zigzag hair is reduced to about 6% which is at least 6-fold less than in wild-type zigzag hair is not restored when the transgene is turned off in adults by the addition of doxicycline, indicating an irreversible role in embryonic stages vision/eye abnormal eyelid morphology (J:99510) eyelids show a ring of yellow hair with slightly thicker skin around the eyelashes than seen in wild-type abnormal meibomian gland morphology (J:86628) enlarged meibomian gland in the absence of doxicycline (transgene is expressed) however, the preputial gland and sweat glands are normal limbs/digits/tail limbs/digits/tail phenotype (J:86628) in the absence of doxicycline (the transgene is expressed), overall tail morphology is indistinguishable from controls
Genotype	Allelic Composition	Genetic Background
tg3	Tg(tetO-BCR/ABL1)27Dgt/0 Tg(MMTVtTA)1Mam/0	involves: C57BL/6 * FVB/N * SJL
life span/aging premature death (J:72377) upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~76 days hematopoietic system anemia (J:72377) severe anemia develops in peripheral blood without TET treatment increased leukocyte cell number (J:72377) increased peripheral blood leukocyte count is observed 10-20 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood decreased platelet cell number (J:72377) severe thrombocytopenia in peripheral blood develops when TET treatment is stopped enlarged spleen (J:72377) spleen becomes massively enlarged when TET treatment is stopped immune system increased leukocyte cell number (J:72377) increased peripheral blood leukocyte count is observed 10-20 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood enlarged spleen (J:72377) spleen becomes massively enlarged when TET treatment is stopped enlarged lymph nodes (J:72377) nodes become massively enlarged when TET is stopped; when TET is given to mice in advanced stages of disease, complete regression of enlarged lymph nodes occurs within 5 days cellular increased apoptosis (J:72377) resumption of TET treatment results in ~80% of leukemic cells undergoing apoptosis skeleton abnormal bone marrow morphology (J:72377) bone marrow is pale; hematopoietic cells are replaced by lymphoblasts tumorigenesis leukemia (J:72377) 100% of mice develop acute lymphoblastic leukemia (ALL) upon withdrawal of tetracycline administration leukocyte counts range from 80000-150000/ul leukemic cells infiltrate skin, pleura, and meninges
Genotype	Allelic Composition	Genetic Background
tg4	Tg(tetO-BCR/ABL1)2Dgt/0 Tg(MMTVtTA)1Mam/0	involves: C57BL/6 * FVB/N * SJL
life span/aging premature death (J:72377) upon withdrawal of tetracycline (TET), expression of BCR/ABL results in development of lethal leukemia; 100% of bitransgenic mice die by ~27 days hematopoietic system anemia (J:72377) severe anemia develops in peripheral blood without TET treatment increased leukocyte cell number (J:72377) increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood decreased platelet cell number (J:72377) severe thrombocytopenia in peripheral blood develops when TET treatment is stopped enlarged spleen (J:72377) spleen becomes massively enlarged when TET treatment is stopped immune system increased leukocyte cell number (J:72377) increased peripheral blood leukocyte count is observed 6-10 days after TET withdrawal; blood shows presence of cells resembling immature lymphocytes when TET is given to mice in advanced stages of disease, WBC counts normalize in 48-72 hours, lymphoblasts are not detected in peripheral blood enlarged spleen (J:72377) spleen becomes massively enlarged when TET treatment is stopped enlarged lymph nodes (J:72377) nodes become massively enlarged when TET is stopped; when TET is given to mice in advanced stages of disease, complete regression of enlarged lymph nodes occurs within 5 days cellular increased apoptosis (J:72377) spleen becomes massively enlarged skeleton abnormal bone marrow morphology (J:72377) bone marrow is pale; hematopoietic cells are replaced by lymphoblasts tumorigenesis leukemia (J:72377) 100% of mice develop acute lymphoblastic leukemia (ALL) upon withdrawal of tetracycline administration leukocyte counts range from 80000-150000/ul leukemic cells infiltrate skin, pleura, and meninges
Genotype	Allelic Composition	Genetic Background
tg5	Eda^Ta-6J/Y Tg(MMTVtTA)1Mam/0 Tg(tetO-Eda*A1)1Dsch/0	involves: C57BL/6J
growth/size decreased body weight (J:86628) at 5 months of age, weight is about 80% of wild-type in the absence of doxicycline skin/coat/nails abnormal coat/ hair morphology (J:86628) in the presence of doxicycline throughout embryonic development to suppress Eda-A1 transgene expression, males are identical to Eda^Ta-6J males, showing lack of tail hair, guard hair and zigzag hair; mice continue to show this phenotype even after withdrawal of doxicycline from the food at 6 months of age disheveled coat (J:86628) in the absence of doxicycline, mutants have somewhat scruffy disordered coat hair compared to wild-type and Eda^Ta-6J males abnormal hair growth (J:86628) in the absence of doxicycline, tail hairs are reduced in number however, the hair behind the ears that is missing in Eda^Ta-6J males is fully restored when the transgene is expressed (absence of doxicycline) short hair (J:86628) in the absence of doxicycline, tail hairs are reduced in length abnormal hair types (J:86628) in the absence of doxicycline, the number of medium hairs is increased to a similar extent as in Eda^Ta-6J males however, total hair numbers are unchanged absent zigzag hairs (J:86628) zigzag hairs are not restored by transgene expression (absence of doxicycline) however, the number of guard hairs is restored to wild-type levels abnormal skin morphology (J:86628) tail ridges on skin surfaces are absent in the absence of doxicycline endocrine/exocrine glands abnormal gland morphology (J:86628) in the presence of doxicycline throughout embryonic development to suppress Eda-A1 transgene expression, males are identical to Eda^Ta-6J males, showing lack of sweat glands; mice continue to show this phenotype even after withdrawal of doxicycline from the food at 6 months of age abnormal sebaceous gland morphology (J:99510) transgene expression results in hypertrophy of sebaceous glands associated with hair follicles of the eyelids absent meibomian glands (J:99510, J:86628) meibomian glands are not restored by transgene expression (J:86628) however, Eda transgene expression does restore the sweat glands that are absent in Eda^Ta-6J males (J:86628) abnormal preputial gland morphology (J:86628) preputial gland is not restored by transgene expression enlarged sebaceous gland (J:86628) in the absence of doxicycline, sebaceous glands are 200-300% larger than in wild-type or Eda^Ta-6J males; size of individual sebocytes is the same but the numbers are increased, with excessive production of sebum hyperplasia is seen in both glands associated with each de novo guard follicle and also in the single sebaceous gland associated with each medium follicle addition of doxicycline at 3 months of age reverses the hyperplasia of sebaceous glands within 3 months vision/eye absent meibomian glands (J:99510, J:86628) meibomian glands are not restored by transgene expression (J:86628) however, Eda transgene expression does restore the sweat glands that are absent in Eda^Ta-6J males (J:86628) immune system immune system phenotype (J:99510) transgene expression rescues the susceptibility to corneal inflammation seen in Eda^Ta-6J males reproductive system abnormal preputial gland morphology (J:86628) preputial gland is not restored by transgene expression renal/urinary system abnormal preputial gland morphology (J:86628) preputial gland is not restored by transgene expression

Notes

Additional lines were generated and showed comparable tissue expression patterns.

When transgenic mice were mated to mice transgenic for either lacZ or luciferase reporter genes coupled to tetracycline-responsive promoter elements (TRE), nearly uniform expression of the reporter was found in seminal vesicle, salivary gland, and Leydig cells of the double transgenic offspring. More heterogeneous patterns of reporter expression were observed in mammary epithelial cells and basal cells of the epidermis. Lower levels of reporter gene expression were also observed in a broad range of tissues. Transcriptional activation mediated by tTA was up to several hundredfold and was abrogated after the administration of tetracycline.

In combination with Tg(BCR/ABL1)2Dgt, when tetracycline administration is stopped, bitransgenic mice are models for B cell acute lymphoblastic leukemia (ALL). (J:72377)

References

Original:	J:92586 Hennighausen L et al., "Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system." J Cell Biochem 1995 Dec;59(4):463-72
All:	13 reference(s)

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