Phenotypes associated with this allele

• Allele Symbol: Id3^tm1Zhu
• Allele Name: targeted mutation 1, Yuan Zhuang
• Allele ID: MGI:2679967
• Summary: 13 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Id3^tm1Zhu/Id3^tm1Zhu	B6.129S4-Id3^tm1Zhu	MGI:5009811
hm2	Id3^tm1Zhu/Id3^tm1Zhu	involves: 129S4/SvJaeSor	MGI:5000526
hm3	Id3^tm1Zhu/Id3^tm1Zhu	involves: 129S4/SvJaeSor * C57BL/6	MGI:3831664
hm4	Id3^tm1Zhu/Id3^tm1Zhu	involves: 129/Sv * C57BL/6	MGI:2680043
cn5	Gt(ROSA)26Sor^tm1(cre/ERT2)Thl/Gt(ROSA)26Sor^+ Id1^tm3Bene/Id1^tm3Bene Id2^tm1Xdz/Id2^tm1Xdz Id3^tm1Zhu/Id3^tm1Zhu	involves: 129S4/SvJaeSor * C57BL/6	MGI:5428955
cn6	Id1^tm3Bene/Id1^tm3Bene Id2^tm1Xdz/Id2^+ Id3^tm1Zhu/Id3^tm1Zhu Tg(Nes-cre)1Kln/0	involves: 129S4/SvJaeSor * C57BL/6 * SJL	MGI:5428947
cn7	Id1^tm3Bene/Id1^tm3Bene Id2^tm1Xdz/Id2^tm1Xdz Id3^tm1Zhu/Id3^tm1Zhu Tg(Nes-cre)1Kln/0	involves: 129S4/SvJaeSor * C57BL/6 * SJL	MGI:5428946
cx8	Id1^tm1Zhu/Id1^tm1Zhu Id3^tm1Zhu/Id3^tm1Zhu	either: (involves: 129S1/Sv * 129S4/SvJaeSor) or (involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6)	MGI:5000527
cx9	Id1^tm1Zhu/Id1^+ Id3^tm1Zhu/Id3^tm1Zhu	involves: 129S1/Sv * 129S4/SvJaeSor	MGI:5000531
cx10	Id1^tm1Zhu/Id1^tm1Zhu Id3^tm1Zhu/Id3^+	involves: 129S1/Sv * 129S4/SvJaeSor	MGI:5002366
cx11	Id1^tm1Zhu/Id1^tm1Zhu Id3^tm1Zhu/Id3^tm1Zhu	involves: 129S1/Sv * 129S4/SvJaeSor	MGI:5000530
cx12	Id1^tm1Zhu/Id1^+ Id3^tm1Zhu/Id3^+ Twist1^tm1Bhr/Twist1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:5000537
cx13	Id1^tm1Zhu/Id1^tm1Zhu Id3^tm1Zhu/Id3^+ Twist1^tm1Bhr/Twist1^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd	MGI:5000538

Genotype
MGI:5009811

hm1

• Allelic Composition: Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: B6.129S4-Id3^tm1Zhu

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

endocrine/exocrine glands

decreased salivation ( J:93916 )

• as early as 2 months of age

digestive/alimentary system

decreased salivation ( J:93916 )

• as early as 2 months of age

vision/eye

decreased tear production ( J:93916 )

• as early as 2 months of age, mice exhibit reduced tear production compared with wild-type mice

homeostasis/metabolism

decreased salivation ( J:93916 )

• as early as 2 months of age

Genotype
MGI:5000526

hm2

• Allelic Composition: Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129S4/SvJaeSor

reproductive system

reproductive system phenotype ( J:44278 )

N • mice are healthy and fertile

endocrine/exocrine glands

decreased salivation ( J:93916 )

• as early as 2 to 4 months of age

• however, thymectomy rescues defect

salivary gland inflammation ( J:93916 )

• as early as 2 months of age and increasing in severity with age

abnormal lacrimal gland morphology ( J:93916 )

• aged mice exhibit destruction of lacrimal gland tissue with opaque spots unlike wild-type mice

lacrimal gland inflammation ( J:93916 )

• as early as 2 months of age prior to eye abnormalities

immune system

immune system phenotype ( J:93916 )

N • peripheral lymphocytes are normal

salivary gland inflammation ( J:93916 )

• as early as 2 months of age and increasing in severity with age

lacrimal gland inflammation ( J:93916 )

• as early as 2 months of age prior to eye abnormalities

increased autoantibody level ( J:93916 )

• at 1 year of age, mice exhibit increased levels of SSA and SSB autoantibodies compared with wild-type mice

vision/eye

lacrimal gland inflammation ( J:93916 )

• as early as 2 months of age prior to eye abnormalities

abnormal eye morphology ( J:93916 )

• at 6 to 10 months of age, 13 of 102 mice exhibit difficulties in maintaining fully opened eyelids due to skin lesions around the eyes unlike wild-type mice

• after 1 year, 35 of 41 mice exhibit eye abnormalities compared with wild-type mice

abnormal lacrimal gland morphology ( J:93916 )

• aged mice exhibit destruction of lacrimal gland tissue with opaque spots unlike wild-type mice

decreased tear production ( J:93916 )

• as early as 2 to 4 months of age, mice exhibit reduced tear production compared with wild-type mice

• however, thymectomy rescues defect

digestive/alimentary system

decreased salivation ( J:93916 )

• as early as 2 to 4 months of age

• however, thymectomy rescues defect

salivary gland inflammation ( J:93916 )

• as early as 2 months of age and increasing in severity with age

homeostasis/metabolism

decreased salivation ( J:93916 )

• as early as 2 to 4 months of age

• however, thymectomy rescues defect

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:93916

Genotype
MGI:3831664

hm3

• Allelic Composition: Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

hematopoietic system

abnormal T cell differentiation ( J:144696 )

• serial transplant of mutant bone marrow into irradiated hosts reveals a defect in thymocyte progenitors

• secondary transplant of mutant bone marrow leads to an 8-fold reduction in the thymocytes compared to controls 5 weeks after engraftment, and 3-fold less thymocytes are present 12 days after engraftment

• increasing number of bone marrow cells transplanted still fail to rescue the defect suggesting a defect occurs during T cell development

immune system

abnormal T cell differentiation ( J:144696 )

• serial transplant of mutant bone marrow into irradiated hosts reveals a defect in thymocyte progenitors

• secondary transplant of mutant bone marrow leads to an 8-fold reduction in the thymocytes compared to controls 5 weeks after engraftment, and 3-fold less thymocytes are present 12 days after engraftment

• increasing number of bone marrow cells transplanted still fail to rescue the defect suggesting a defect occurs during T cell development

Genotype
MGI:2680043

hm4

• Allelic Composition: Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129/Sv * C57BL/6

immune system

immune system phenotype ( J:56950 )

N • normal numbers of splenocytes and thymocytes

N • basal levels of IgM, IgG2b, IgG3, and IgA are normal; after challenge IgM, IgG1, IgG2b, IgA levels are as expected

decreased B cell proliferation ( J:56950 )

• reduced response to anti-IgM

decreased immunoglobulin level ( J:56950 )

• basal levels of IgG1 and IgG2a reduced to 1/2 normal

• after primary challenge, IgG2a and IgG3 levels about 1/10 normal

• after secondary challenge, levels are 1/15 normal

• when challenged with DNP-Ficoll, specific IgM and IgA levels 1/10 normal

abnormal T cell physiology ( J:56950 )

• IFN-gamma expression reduced after T-cell stimulation

hematopoietic system

decreased B cell proliferation ( J:56950 )

• reduced response to anti-IgM

decreased immunoglobulin level ( J:56950 )

• basal levels of IgG1 and IgG2a reduced to 1/2 normal

• after primary challenge, IgG2a and IgG3 levels about 1/10 normal

• after secondary challenge, levels are 1/15 normal

• when challenged with DNP-Ficoll, specific IgM and IgA levels 1/10 normal

abnormal T cell physiology ( J:56950 )

• IFN-gamma expression reduced after T-cell stimulation

cellular

decreased B cell proliferation ( J:56950 )

• reduced response to anti-IgM

Genotype
MGI:5428955

cn5

• Allelic Composition: Gt(ROSA)26Sor^{tm1(cre/ERT2)Thl}/Gt(ROSA)26Sor⁺; Id1^tm3Bene/Id1^tm3Bene; Id2^tm1Xdz/Id2^tm1Xdz; Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

cellular

premature neuronal precursor differentiation ( J:185426 )

• following tamoxifen-treatment of cultured neural stem cells

nervous system

premature neuronal precursor differentiation ( J:185426 )

• following tamoxifen-treatment of cultured neural stem cells

Genotype
MGI:5428947

cn6

• Allelic Composition: Id1^tm3Bene/Id1^tm3Bene; Id2^tm1Xdz/Id2⁺; Id3^tm1Zhu/Id3^tm1Zhu; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * SJL

nervous system

nervous system phenotype ( J:185426 )

N • neural stem cells exhibit normal self-renewal and proliferation

Genotype
MGI:5428946

cn7

• Allelic Composition: Id1^tm3Bene/Id1^tm3Bene; Id2^tm1Xdz/Id2^tm1Xdz; Id3^tm1Zhu/Id3^tm1Zhu; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * SJL

mortality/aging

neonatal lethality, incomplete penetrance ( J:185426 )

• nearly all mice die within the first 24 hours after birth

nervous system

abnormal neuron differentiation ( J:185426 )

• at E18.5, neuronal stem cells exhibit altered shape at the apical border compared with control cells

• cultured neural stem cells fail to form primary and secondary neurospheres unlike control cells

premature neuronal precursor differentiation ( J:185426 )

• of neural stem cells in vitro and in vivo as determined by marker expression

abnormal neuronal precursor proliferation ( J:185426 )

• at E18.5, neural stem cell proliferation is reduced with prolonged cell cycle timing and increased probability of exiting the cell cycle compared with control cells

abnormal brain morphology ( J:185426 )

• hypocellular at E18.5 and P0

abnormal cortical ventricular zone morphology ( J:185426 )

• disrupted pseudo-stratified architecture at E18.5

thin external granule cell layer ( J:185426 )

• at E18.5 and P0

enlarged brain ventricles ( J:185426 )

• at E18.5 and P0

cellular

abnormal cell cycle ( J:185426 )

• at E18.5, neural stem cell proliferation is reduced with prolonged cell cycle timing and increased probability of exiting the cell cycle compared with control cells

abnormal neuron differentiation ( J:185426 )

• at E18.5, neuronal stem cells exhibit altered shape at the apical border compared with control cells

• cultured neural stem cells fail to form primary and secondary neurospheres unlike control cells

premature neuronal precursor differentiation ( J:185426 )

• of neural stem cells in vitro and in vivo as determined by marker expression

abnormal neuronal precursor proliferation ( J:185426 )

• at E18.5, neural stem cell proliferation is reduced with prolonged cell cycle timing and increased probability of exiting the cell cycle compared with control cells

Genotype
MGI:5000527

cx8

• Allelic Composition: Id1^tm1Zhu/Id1^tm1Zhu; Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: either: (involves: 129S1/Sv * 129S4/SvJaeSor) or (involves: 129S1/Sv * 129S4/SvJaeSor * C57BL/6)

mortality/aging

preweaning lethality, complete penetrance ( J:44278 )

• mice are not viable

Genotype
MGI:5000531

cx9

• Allelic Composition: Id1^tm1Zhu/Id1⁺; Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor

immune system

increased susceptibility to otitis media ( J:311050 )

• 71% of mice are affected with middle ear fluid, inflammation in the tympanic membrane and opacification of the tympanic membrane, indicating otitis media

• inflammatory cells of the effusion content are mainly polymorphonuclear cells

cardiovascular system

abnormal tumor vascularization ( J:86480 )

• injected B6RV2 and LLC tumors exhibit impaired angiogenesis compared to when tumors are injected into wild-type mice

hearing/vestibular/ear

abnormal middle ear morphology ( J:311050 )

• fibrous proliferation is seen in the middle ear space of some mice and the middle ear mucosa is thickened

middle ear effusion ( J:311050 )

• different degrees of effusion in the middle ear cavities

increased or absent threshold for auditory brainstem response ( J:311050 )

• 100% of mice exhibit high ABR thresholds for at least one stimulus frequency in at least one ear, with 92.9% for the right ears and 92.9% for the left ears

• at P30, the mean ABR thresholds at any stimulus frequency are higher than of controls and at P60, ABR thresholds at all stimulus frequencies are higher

decreased distortion product otoacoustic emission amplitude ( J:311050 )

• at P30 and P60, the DPOAE amplitudes at dominant frequencies 7,692, 10,152, 13,390, and 17,672 are lower

conductive hearing loss ( J:311050 )

• mice present hearing loss from 30 days of age at all stimulus frequencies

increased susceptibility to otitis media ( J:311050 )

• 71% of mice are affected with middle ear fluid, inflammation in the tympanic membrane and opacification of the tympanic membrane, indicating otitis media

• inflammatory cells of the effusion content are mainly polymorphonuclear cells

neoplasm

abnormal tumor vascularization ( J:86480 )

• injected B6RV2 and LLC tumors exhibit impaired angiogenesis compared to when tumors are injected into wild-type mice

decreased metastatic potential ( J:86480 )

• injected B6RV2 and LCC tumors exhibit decreased metastases compared to when tumors are injected into wild-type mice

decreased tumor growth/size ( J:86480 )

• injected B6RV2, B-CA, and LCC tumors exhibit impaired tumor growth compared to when tumors are injected into wild-type mice

tumor regression ( J:86480 )

• injected B6RV2 and B-CA tumors exhibit tumor regression compared to when tumors are injected into wild-type mice

homeostasis/metabolism

middle ear effusion ( J:311050 )

• different degrees of effusion in the middle ear cavities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:311050

Genotype
MGI:5002366

cx10

• Allelic Composition: Id1^tm1Zhu/Id1^tm1Zhu; Id3^tm1Zhu/Id3⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor

immune system

increased susceptibility to otitis media ( J:311050 )

• 51% of mice are affected with middle ear fluid, inflammation in the tympanic membrane and opacification of the tympanic membrane, indicating otitis media

• inflammatory cells of the effusion content are mainly polymorphonuclear cells

hearing/vestibular/ear

abnormal middle ear morphology ( J:311050 )

• fibrous proliferation is seen in the middle ear space of some mice and the middle ear mucosa is generally thickened

middle ear effusion ( J:311050 )

• different degrees of effusion in the middle ear cavities

increased or absent threshold for auditory brainstem response ( J:311050 )

• 89.1% of mice exhibit high ABR thresholds for at least one stimulus frequency in at least one ear, with 82.2% for the right ears and 81.2% for the left ears

• at P30, the mean ABR thresholds at any stimulus frequency are higher than of controls and at P60, ABR thresholds for click and 8 kHz are highe

decreased distortion product otoacoustic emission amplitude ( J:311050 )

• at P30, the DPOAE amplitudes at dominant frequencies 7,692, 10,152, 13,390, and 17,672 are lower

• at P60, the DPOAE amplitudes at 13,390 and 17,672 are lower

conductive hearing loss ( J:311050 )

• mice present hearing loss from 30 days of age at all stimulus frequencies

increased susceptibility to otitis media ( J:311050 )

• 51% of mice are affected with middle ear fluid, inflammation in the tympanic membrane and opacification of the tympanic membrane, indicating otitis media

• inflammatory cells of the effusion content are mainly polymorphonuclear cells

homeostasis/metabolism

middle ear effusion ( J:311050 )

• different degrees of effusion in the middle ear cavities

vision/eye

vision/eye phenotype ( J:170418 )

N • retinal development are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:311050

Genotype
MGI:5000530

cx11

• Allelic Composition: Id1^tm1Zhu/Id1^tm1Zhu; Id3^tm1Zhu/Id3^tm1Zhu
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:86480 , J:170418 )

• mice do not survive beyond E13.5 (J:86480)

• however, mice are found in Mendelian ratios at E10.5 (J:86480)

• lethal around E13.5 (J:170418)

nervous system

abnormal brain vasculature morphology ( J:86480 )

• aberrant capillaries flank the cavity that forms near ganglionic eminences

intracranial hemorrhage ( J:86480 )

• at E12.5

premature neuronal precursor differentiation ( J:86480 )

abnormal neuronal precursor proliferation ( J:86480 , J:170418 )

• at E11.5, fewer proliferating cells are present in the neuroepithelium of the telencephalon and rhombencephalon compared to in wild-type mice (J:86480)

• proliferation of neuronal progenitors is increased compared to in wild-type mice (J:170418)

decreased brain size ( J:86480 )

abnormal embryonic/fetal subventricular zone morphology ( J:86480 )

• at E12.5, ganglionic eminences develop cavitational lesions with areas of hypocellularity that coalesce unlike in wild-type mice

• aberrant capillaries flank the cavity

vision/eye

small lens ( J:170418 )

abnormal retina development ( J:170418 )

• at E13.5, embryonic retinal progenitor cells exhibit decreased proliferation compared with wild-type cells

• however, progenitor cell apoptosis is normal

microphthalmia ( J:170418 )

• mice exhibit small eyes with decreased eye axial length and equatorial diameter compared with wild-type mice

retina hypoplasia ( J:170418 )

cardiovascular system

abnormal brain vasculature morphology ( J:86480 )

• aberrant capillaries flank the cavity that forms near ganglionic eminences

decreased angiogenesis ( J:86480 )

• in the brain

intracranial hemorrhage ( J:86480 )

• at E12.5

embryo

decreased embryo weight ( J:86480 )

• at E11.5 and E12.5

growth/size/body

decreased embryo weight ( J:86480 )

• at E11.5 and E12.5

cellular

premature neuronal precursor differentiation ( J:86480 )

abnormal neuronal precursor proliferation ( J:86480 , J:170418 )

• at E11.5, fewer proliferating cells are present in the neuroepithelium of the telencephalon and rhombencephalon compared to in wild-type mice (J:86480)

• proliferation of neuronal progenitors is increased compared to in wild-type mice (J:170418)

Genotype
MGI:5000537

cx12

• Allelic Composition: Id1^tm1Zhu/Id1⁺; Id3^tm1Zhu/Id3⁺; Twist1^tm1Bhr/Twist1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd

skeleton

premature cranial suture closure ( J:108218 )

• 5% penetrance

Genotype
MGI:5000538

cx13

• Allelic Composition: Id1^tm1Zhu/Id1^tm1Zhu; Id3^tm1Zhu/Id3⁺; Twist1^tm1Bhr/Twist1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129S7/SvEvBrd

skeleton

skeleton phenotype ( J:108218 )

N • mice do not exhibit craniosynostosis unlike in Twist1^tm1Bhr heterozygotes