Phenotypes associated with this allele

• Allele Symbol: Tgfb1^tm1Doe
• Allele Name: targeted mutation 1, Thomas Doetschman
• Allele ID: MGI:1857258
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tgfb1^tm1Doe/Tgfb1^tm1Doe	C.129S2-Tgfb1^tm1Doe	MGI:3721949
hm2	Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas	MGI:5008272
hm3	Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * BALB/c * CF-1	MGI:2657029
hm4	Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * CF-1	MGI:2174925
ht5	Tgfb1^tm1Doe/Tgfb1^+	involves: 129S2/SvPas * CF-1	MGI:2174926
cn6	Tgfb1^tm1Doe/Tgfb1^tm2.1Doe Tg(Lck-cre)548Jxm/?	involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * BALB/c * C57BL/6 * CBA	MGI:3849995
cx7	Ifng^tm1Ts/Ifng^tm1Ts Tgfb1^tm1Doe/Tgfb1^tm1Doe	C.129-Ifng^tm1Ts Tgfb1^tm1Doe	MGI:3721950
cx8	Il4^tm2Nnt/Il4^tm2Nnt Tgfb1^tm1Doe/Tgfb1^tm1Doe	C.Cg-Tgfb1^tm1Doe Il4^tm2Nnt	MGI:3721951
cx9	Prkdc^scid/Prkdc^scid Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129 * C3H * CF-1	MGI:4361478
cx10	Foxn1^nu/Foxn1^nu Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * BALB/c * CF-1	MGI:3622470
cx11	Cd8a^tm1Mak/Cd8a^tm1Mak Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * C57BL/6 * CF-1	MGI:3622472
cx12	Ighm^tm1Cgn/Ighm^+ Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * C57BL/6 * CF-1	MGI:3622466
cx13	Ighm^tm1Cgn/Ighm^tm1Cgn Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S2/SvPas * C57BL/6 * CF-1	MGI:3622465
cx14	Cd4^tm1Knw/Cd4^tm1Knw Tgfb1^tm1Doe/Tgfb1^tm1Doe	involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CF-1	MGI:3622474

Genotype
MGI:3721949

hm1

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: C.129S2-Tgfb1^tm1Doe

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:69346 )

• mice survive average of 13.1 days after birth (range 8.5-39.5 days), longer than on mixed background

prenatal lethality, incomplete penetrance ( J:69346 )

• Background Sensitivity: ratio of homozygous to wild-type pups born is 0.24, in contrast to expected ratio of 1; more severe than on mixed background

liver/biliary system

hepatic necrosis ( J:69346 )

• widespread hepatocyte necrosis is seen at 11-12 days

liver inflammation ( J:69346 )

• Background Sensitivity: extensive inflammation is observed in 11-12 day-old mice, while livers of mice on the 129/BALB/c/CF1 background appear normal at this age

immune system

heart inflammation ( J:69346 )

• inflammatory lesions are seen

decreased CD4-positive, alpha-beta T cell number ( J:69346 )

• Cd4+ T cells in spleen are ~half the number in control mice

increased CD4-positive, alpha-beta T cell number ( J:69346 )

• CD4+ T cells are ~7-fold more abundant in the liver compared to controls

increased T-helper 1 cell number ( J:69346 )

• livers contain abnormally high numbers of activated/effector Th1 cells

increased interferon-gamma secretion ( J:69346 )

• liver CD4+ T cells in vitro produce large amounts of interferon gamma Ifng

liver inflammation ( J:69346 )

• Background Sensitivity: extensive inflammation is observed in 11-12 day-old mice, while livers of mice on the 129/BALB/c/CF1 background appear normal at this age

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:69346 )

• Cd4+ T cells in spleen are ~half the number in control mice

increased CD4-positive, alpha-beta T cell number ( J:69346 )

• CD4+ T cells are ~7-fold more abundant in the liver compared to controls

increased T-helper 1 cell number ( J:69346 )

• livers contain abnormally high numbers of activated/effector Th1 cells

cardiovascular system

heart inflammation ( J:69346 )

• inflammatory lesions are seen

homeostasis/metabolism

increased circulating alanine transaminase level ( J:69346 )

• Background Sensitivity: bs levels are elevated in plasma of 8/10 11-14 day old mice

cellular

hepatic necrosis ( J:69346 )

• widespread hepatocyte necrosis is seen at 11-12 days

Genotype
MGI:5008272

hm2

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas

nervous system

nervous system phenotype ( J:117465 )

N • mice exhibit normal numbers of dopaminergic neurons

Genotype
MGI:2657029

hm3

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * BALB/c * CF-1

mortality/aging

postnatal lethality, complete penetrance ( J:69346 )

• Background Sensitivity: mice survive average of 20.1 days after birth (range 8.5 - 39.5 days); rate of postnatal lethality is more severe on BALB/c background compared to 129/CF1 background

prenatal lethality, incomplete penetrance ( J:69346 )

• Background Sensitivity: bs ratio of homozygous to wild-type pups born is 0.64, in contrast to expected ratio of 1; less severe than on inbred BALB/c background

liver/biliary system

liver/biliary system phenotype ( J:69346 )

N • Background Sensitivity: at 11-12 days, livers appear normal relative to normal littermates

liver inflammation ( J:69346 )

• Background Sensitivity: mice show mild periportal inflammation and no hepatocyte loss compared to animals on congenic BALB/c background

immune system

heart inflammation ( J:69346 )

• inflammatory lesions

increased interferon-gamma secretion ( J:69346 )

• liver CD4+ T cells in vitro produce large amounts of interferon gamma Ifng

liver inflammation ( J:69346 )

• Background Sensitivity: mice show mild periportal inflammation and no hepatocyte loss compared to animals on congenic BALB/c background

lung inflammation ( J:69346 )

• inflammatory lesions

cardiovascular system

heart inflammation ( J:69346 )

• inflammatory lesions

respiratory system

lung inflammation ( J:69346 )

• inflammatory lesions

homeostasis/metabolism

increased circulating alanine transaminase level ( J:69346 )

• Background Sensitivity: levels are elevated in plasma of 1/10 mice; incidence is lower than on BALB/c background

Genotype
MGI:2174925

hm4

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * CF-1

cellular

myocardium necrosis ( J:2892 )

• variable degrees are observed

gastric necrosis ( J:2892 )

• variable degrees are observed

multifocal hepatic necrosis ( J:2892 )

• seen in some animals

mortality/aging

lethality at weaning, complete penetrance ( J:2892 , J:99033 )

• mice die around 3 weeks of age from wasting (J:2892)

• due to multifocal inflammation, median survival of mutant mice is 21 days (J:99033)

growth/size/body

cachexia ( J:2892 )

• at ~3 weeks of age, mice exhibit severe wasting

hematopoietic system

increased leukocyte cell number ( J:2892 )

• average number of white blood cells is usually elevated in mutants

small spleen ( J:2892 )

• in most animals, spleens are smaller than in controls

immune system

increased leukocyte cell number ( J:2892 )

• average number of white blood cells is usually elevated in mutants

small spleen ( J:2892 )

• in most animals, spleens are smaller than in controls

abnormal Peyer's patch germinal center morphology ( J:2892 )

• Peyer's patches possess less distinct germinal centers compared to normal controls

decreased Peyer's patch number ( J:2892 )

• Peyer's patches are fewer than normal

enlarged lymph nodes ( J:2892 )

• >60% of mice have slightly enlarged lymph nodes

abnormal inflammatory response ( J:2892 )

• mild to moderate inflammation of serosa of internal organs (stomach, intestine, kidney, ovary, and testis) is seen in some mice

heart inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation; in some animals, inflammation involves pericardium, myocardium and endocardium of atria and ventricles

salivary gland inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; primarily (~80%) lymphocytic and plasmacytic inflammation; some degree of multifocal inflammatory cell infiltration is seen in ~50% of animals

stomach inflammation ( J:2892 )

• inflammation is mainly granulocytic (60% neutrophils)

lacrimal gland inflammation ( J:2892 )

pancreas inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; primarily (~80%) lymphocytic and plasmacytic inflammation; some degree of multifocal inflammation is seen in ~50% of animals

brain inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation

diaphragmitis ( J:2892 )

eye inflammation ( J:2892 )

• some mice show conjunctivitis, while others display inflammation of striated ocular muscle, or lacrimal gland inflammation

conjunctivitis ( J:2892 )

• seen in some animals prior to death

liver inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; granulocytes and lymphocytes are ~equal in number

myositis ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation; various muscles (diaphragm, masseter, leg)

lung inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation

skin inflammation ( J:2892 )

• seen in some animals prior to death

liver/biliary system

multifocal hepatic necrosis ( J:2892 )

• seen in some animals

liver inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; granulocytes and lymphocytes are ~equal in number

cardiovascular system

myocardium necrosis ( J:2892 )

• variable degrees are observed

heart inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation; in some animals, inflammation involves pericardium, myocardium and endocardium of atria and ventricles

muscle

myocardium necrosis ( J:2892 )

• variable degrees are observed

diaphragmitis ( J:2892 )

myositis ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation; various muscles (diaphragm, masseter, leg)

abnormal diaphragm morphology ( J:2892 )

• diaphragms show inflammation and necrosis severe enough to interfere with respiration

endocrine/exocrine glands

salivary gland inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; primarily (~80%) lymphocytic and plasmacytic inflammation; some degree of multifocal inflammatory cell infiltration is seen in ~50% of animals

lacrimal gland inflammation ( J:2892 )

pancreas inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; primarily (~80%) lymphocytic and plasmacytic inflammation; some degree of multifocal inflammation is seen in ~50% of animals

digestive/alimentary system

gastric necrosis ( J:2892 )

• variable degrees are observed

gastric ulcer ( J:2892 )

• severe focal ulceration and/or hyperplasia of basal epithelial layer accompanies inflammation; non-glandular portion of stomach in most mice shows some degree of acanthosis and inflammatory cell infiltration

salivary gland inflammation ( J:2892 )

• inflammatory cell infiltration is primarily periductal; primarily (~80%) lymphocytic and plasmacytic inflammation; some degree of multifocal inflammatory cell infiltration is seen in ~50% of animals

stomach inflammation ( J:2892 )

• inflammation is mainly granulocytic (60% neutrophils)

respiratory system

lung inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation

vision/eye

lacrimal gland inflammation ( J:2892 )

eye inflammation ( J:2892 )

• some mice show conjunctivitis, while others display inflammation of striated ocular muscle, or lacrimal gland inflammation

conjunctivitis ( J:2892 )

• seen in some animals prior to death

behavior/neurological

hunched posture ( J:2892 )

• seen in some animals prior to death

nervous system

brain inflammation ( J:2892 )

• primarily (~80%) lymphocytic and plasmacytic inflammation

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:2892 )

N • cytokine levels are comparable to controls

integument

skin inflammation ( J:2892 )

• seen in some animals prior to death

disheveled coat ( J:2892 )

• seen in some animals prior to death

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:2892

Genotype
MGI:2174926

ht5

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1⁺
• Genetic Background: involves: 129S2/SvPas * CF-1

homeostasis/metabolism

increased circulating creatinine level ( J:137529 )

• heterozygotes subjected to renal ischemia-reperfusion (IR) under sevoflurane anesthesia display significantly higher plasma creatinine levels than wild-type mice subjected to renal IR under either sevoflurane or pentobarbital sodium anesthesia

abnormal physiological response to xenobiotic ( J:137529 )

• sevoflurane fails to protect heterozygotes against IR-induced renal tubular necrosis, unlike in wild-type controls

• sevoflurane also fails to protect primary cultures of renal proximal tubules against H2O2-induced necrosis, unlike in wild-type controls

increased susceptibility to kidney reperfusion injury ( J:137529 )

• heterozygotes are not protected against renal IR injury under anesthesia with sevoflurane (a volatile anesthetic), unlike similarly treated wild-type controls

renal/urinary system

renal tubular necrosis ( J:137529 )

• heterozygotes subjected to renal IR injury under sevoflurane anesthesia exhibit more severe renal tubular necrosis than similarly treated wild-type controls

• in culture, sevoflurane-treated proximal tubule cells isolated from heterozygous mice are not protected against H2O2-induced necrosis, unlike similarly treated wild-type proximal tubule cells

increased susceptibility to kidney reperfusion injury ( J:137529 )

• heterozygotes are not protected against renal IR injury under anesthesia with sevoflurane (a volatile anesthetic), unlike similarly treated wild-type controls

cellular

renal tubular necrosis ( J:137529 )

• heterozygotes subjected to renal IR injury under sevoflurane anesthesia exhibit more severe renal tubular necrosis than similarly treated wild-type controls

• in culture, sevoflurane-treated proximal tubule cells isolated from heterozygous mice are not protected against H2O2-induced necrosis, unlike similarly treated wild-type proximal tubule cells

Genotype
MGI:3849995

cn6

• Allelic Composition: Tgfb1^tm1Doe/Tgfb1^tm2.1Doe; Tg(Lck-cre)548Jxm/?
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * Black Swiss * BALB/c * C57BL/6 * CBA

Lung and salivary gland inflammation in Tgfb1^tm2.1Doe/Tgfb1^tm2.1Doe Tg(Lck-cre)548Jxm/? (b,e) and Tgfb1^tm1Doe/Tgfb1^tm2.1Doe Tg(Lck-cre)548Jxm/? (c,f) mice

immune system

salivary gland inflammation ( J:150024 )

• salivary gland inflammation is observed in mice at 5 months of age

lung inflammation ( J:150024 )

• inflammation is observed in the lungs at 5 months of age

respiratory system

lung inflammation ( J:150024 )

• inflammation is observed in the lungs at 5 months of age

digestive/alimentary system

salivary gland inflammation ( J:150024 )

• salivary gland inflammation is observed in mice at 5 months of age

endocrine/exocrine glands

salivary gland inflammation ( J:150024 )

• salivary gland inflammation is observed in mice at 5 months of age

Genotype
MGI:3721950

cx7

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: C.129-Ifng^tm1Ts Tgfb1^tm1Doe

mortality/aging

premature death ( J:69346 )

• mice survive average of 32.9 days (range 23-66 days)

growth/size/body

decreased body weight ( J:69346 )

• mice are smaller than littermate controls

cachexia ( J:69346 )

liver/biliary system

liver/biliary system phenotype ( J:69346 )

N • outwardly, livers show no visible abnormalities

liver inflammation ( J:69346 )

• on necropsy, modest inflammatory expansion around portal tracts is observed in some animals

immune system

liver inflammation ( J:69346 )

• on necropsy, modest inflammatory expansion around portal tracts is observed in some animals

homeostasis/metabolism

increased circulating alanine transaminase level ( J:69346 )

• in 4/5 mice >21 days of age, ALT plasma levels are elevated

Genotype
MGI:3721951

cx8

• Allelic Composition: Il4^tm2Nnt/Il4^tm2Nnt; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: C.Cg-Tgfb1^tm1Doe Il4^tm2Nnt

mortality/aging

postnatal lethality, complete penetrance ( J:69346 )

• average survival is 13.6 days (range 10-19.5 days)

homeostasis/metabolism

increased circulating alanine transaminase level ( J:69346 )

• extensive inflammation is observed

immune system

liver inflammation ( J:69346 )

liver/biliary system

liver inflammation ( J:69346 )

Genotype
MGI:4361478

cx9

• Allelic Composition: Prkdc^scid/Prkdc^scid; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129 * C3H * CF-1

cellular

oligozoospermia ( J:129629 )

♂ • 3 of 23 male homozygotes show a significant reduction in total epididymal sperm count (less than 10⁵ sperm) relative to control littermates

♂ • however, remaining homozygotes show only a modest reduction in epididymal sperm count relative to control littermates

abnormal spermatid morphology ( J:129629 )

♂ • 1 of 8 male homozygotes display decreased numbers of elongated spermatids

growth/size/body

decreased body size ( J:129629 )

♂ • male homozygotes are smaller than wild-type and heterozygous control littermates

decreased body weight ( J:129629 )

♂ • between 5 and 10 weeks of age, male homozygotes weigh ~20% less than age-matched control littermates

increased lung weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 50% increase in lung weight relative to body weight

reproductive system

reproductive system phenotype ( J:129629 )

♂N • at 10 weeks of age, male homozygotes show no differences in the wet weight of testis, seminal vesicle or penis relative to body weight

♂N • in addition, male homozygotes display an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes

small seminiferous tubules ( J:129629 )

♂ • male homozygotes exhibit a small but significant reduction in mean tubule diameter relative to control littermates

♂ • however, no consistent relationship between reduced tubule diameter and quality of spermatogenesis is observed

decreased testes secretion ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 95% reduction in mean intratesticular testosterone levels relative to control littermates

abnormal spermatogenesis ( J:129629 )

♂ • 1 of 8 male homozygotes display a large proportion of tubules containing only spermatogonia or spermatocytes and no mature elongated spermatids; however, the majority (7 of 8) homozygotes display normal spermatogenesis

♂ • reduced sperm count and impaired spermatogenesis is highly correlated with reduced body weight

oligozoospermia ( J:129629 )

♂ • 3 of 23 male homozygotes show a significant reduction in total epididymal sperm count (less than 10⁵ sperm) relative to control littermates

♂ • however, remaining homozygotes show only a modest reduction in epididymal sperm count relative to control littermates

abnormal spermatid morphology ( J:129629 )

♂ • 1 of 8 male homozygotes display decreased numbers of elongated spermatids

male infertility ( J:129629 )

♂ • all adult male homozygotes fail to sire pregnancies in naturally cycling adult B10 females over a 3-week mating trial

♂ • however, epididymal sperm from male homozygotes with a normal sperm count are viable and developmentally competent, as shown by in vitro fertilization of oocytes with development of blastocysts occurring at the expected rate

♂ • exogenous testosterone treatments fail to restore the infertility phenotype as indicated by the absence of vaginal plugs, sperm-positive vaginal smears, or evidence of pseudopregnancy in normal adult females

failure of ejaculation ( J:129629 )

♂ • although male homozygotes display avid interest in females and engage in mounting activity, none of 6 males tested attain ejaculation during the 2-hr test period

♂ • however, erectile reflexes and ejaculation can be induced by electrical stimulation in ~50% of males regardless of genotype

homeostasis/metabolism

decreased circulating testosterone level ( J:129629 )

♂ • at both 6- and 10-weeks of age, male homozygotes show a 78% reduction in mean serum testosterone levels relative to wild-type controls

♂ • at 10 weeks of age, male homozygotes also show a 64% reduction in mean serum androstendione levels relative to control littermates; however, mean serum estradiol levels remain unaffected

♂ • exogenous testosterone treatments of both neonatal and adult male homozygotes result in normal serum testosterone levels but fail to alleviate the infertility phenotype

decreased circulating follicle stimulating hormone level ( J:129629 )

♂ • after 15 min cocaging with a cycling female, adult male homozygotes display significantly lower serum FSH levels than control littermates; however, FSH levels are not as severely reduced as LH leves

decreased circulating luteinizing hormone level ( J:129629 )

♂ • after 15 min cocaging with a cycling female, adult male homozygotes display significantly lower serum LH levels than control littermates

behavior/neurological

failure of copulatory plug deposition ( J:129629 )

♂ • no vaginal plugs or sperm-positive vaginal smears are ever observed in any females housed with homozygous mutant males

reduced male mating frequency ( J:129629 )

♂ • when introduced to a receptive female, all (6 of 6) male homozygotes initially engage in normal anogenital investigation; however, only 4 of 6 display mounting activity and only 2 of 6 proceeded to intromission

♂ • in both cases, intromission events are brief and not sustained to ejaculation

♂ • testosterone replacement fails to restore mating competence

endocrine/exocrine glands

small seminiferous tubules ( J:129629 )

♂ • male homozygotes exhibit a small but significant reduction in mean tubule diameter relative to control littermates

♂ • however, no consistent relationship between reduced tubule diameter and quality of spermatogenesis is observed

decreased testes secretion ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 95% reduction in mean intratesticular testosterone levels relative to control littermates

respiratory system

increased lung weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 50% increase in lung weight relative to body weight

immune system

decreased spleen weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 60% decrease in spleen weight relative to body weight

hematopoietic system

decreased spleen weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 60% decrease in spleen weight relative to body weight

adipose tissue

decreased retroperitoneal fat pad weight ( J:129629 )

♂ • at 10 weeks of age, male homozygotes show a 40% decrease in peritoneal fat weight relative to body weight

Genotype
MGI:3622470

cx10

• Allelic Composition: Foxn1^nu/Foxn1^nu; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * BALB/c * CF-1

mortality/aging

premature death ( J:99033 )

• double mutants survive beyond 2 months compared to 21 days for Tgfb1 null mice (3-4 month increase in longevity)

immune system

abnormal T cell physiology ( J:99033 )

• animals have a severe reduction of CD4+ and CD8+ T cells

decreased inflammatory response ( J:99033 )

• organ inflammation is prevented compared to single mutants

hematopoietic system

abnormal T cell physiology ( J:99033 )

• animals have a severe reduction of CD4+ and CD8+ T cells

Genotype
MGI:3622472

cx11

• Allelic Composition: Cd8a^tm1Mak/Cd8a^tm1Mak; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CF-1

mortality/aging

premature death ( J:99033 )

• majority of double mutants die by 35 days of age

Genotype
MGI:3622466

cx12

• Allelic Composition: Ighm^tm1Cgn/Ighm⁺; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CF-1

cellular

increased cell proliferation ( J:99033 )

• splenocytes of Day 12-19 mutants are hyperresponsive to LPS stimulation in culture compared to Igh-6 heterozygous splenocytes

immune system

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

hematopoietic system

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

endocrine/exocrine glands

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

Genotype
MGI:3622465

cx13

• Allelic Composition: Ighm^tm1Cgn/Ighm^tm1Cgn; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * CF-1

mortality/aging

premature death ( J:99033 )

• mice survive for a median of 35 days

growth/size/body

cachexia ( J:99033 )

• mutants display a wasting syndrome which results in death 2-5 days after the start of weight loss

immune system

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

abnormal inflammatory response ( J:99033 )

• animals develop inflammation similar to that displayed by Tgfb1 nulls, although this is delayed by about 2 weeks

hematopoietic system

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

endocrine/exocrine glands

thymus hypoplasia ( J:99033 )

• animals display decreased thymic cellularity

Genotype
MGI:3622474

cx14

• Allelic Composition: Cd4^tm1Knw/Cd4^tm1Knw; Tgfb1^tm1Doe/Tgfb1^tm1Doe
• Genetic Background: involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CF-1

mortality/aging

premature death ( J:99033 )

• majority of double mutants die by 35 days of age