Phenotypes associated with this allele

• Allele Symbol: Sox9⁺
• Allele Name: wild type
• Allele ID: MGI:2431983
• Summary: 40 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Sox9^tm1(cre/ERT2)Haak/Sox9^+	B6.129S7-Sox9^tm1(cre/ERT2)Haak	MGI:4947115
ht2	Sox9^Bbfc/Sox9^+	C57BL/6J-Sox9^Bbfc/GrsrJ	MGI:5659902
ht3	Sox9^tm1.1Gsr/Sox9^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3581014
ht4	Sox9^tm4Tlu/Sox9^+	involves: 129S4/SvJae * C57BL/6J	MGI:5293346
ht5	Sox9^tm4Tlu/Sox9^+	involves: 129S4/SvJae * CD-1	MGI:5293347
ht6	Sox9^tm1.1Gsr/Sox9^+	involves: 129S4/SvJae * CD-1	MGI:3817222
ht7	Sox9^tm1Crm/Sox9^+	involves: 129S7/SvEvBrd * C57BL/6 * CD-1	MGI:3044095
ht8	Sox9^tm1.2Ksec/Sox9^+	involves: 129S/SvEv * C57BL/6 * FVB/N	MGI:7451325
cn9	Adam17^tm1.2Bbl/Adam17^tm1.2Bbl Sox9^tm3(cre)Crm/Sox9^+	B6.129(SJL)-Sox9^tm3(cre)Crm Adam17^tm1.2Bbl	MGI:6241552
cn10	Sox9^tm3.1Tlu/Sox9^+ Tg(Col2a1-cre)1Bhr/0	either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)	MGI:5560998
cn11	Adam17^tm1.2Bbl/Adam17^tm1.2Bbl Sox9^tm3(cre)Crm/Sox9^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4355046
cn12	Adam17^tm1.2Bbl/Adam17^tm1.2Bbl Il17a^tm1Yiw/Il17a^tm1Yiw Sox9^tm3(cre)Crm/Sox9^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:6241555
cn13	Adam17^tm1.2Bbl/Adam17^tm1.2Bbl Il23a^tm1Dnax/Il23a^tm1Dnax Sox9^tm3(cre)Crm/Sox9^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:6241556
cn14	Sox9^em1(cre/ERT2)Tchn/Sox9^+ Stk26^tm2.1Zzh/Stk26^tm2.1Zzh	involves: 129P2/OlaHsd * C57BL/6	MGI:7491701
cn15	Sox9^tm1Gsr/Sox9^+ Tg(Pdx1-cre)6Cvw/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA * FVB/N	MGI:3817221
cn16	Sox9^tm1Gsr/Sox9^+ Tg(Pax3-cre)1Joe/0	involves: 129P2/OlaHsd * C57BL/6 * NMRI * SJL	MGI:4849537
cn17	Sox9^tm1Gsr/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:3710216
cn18	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Sox9^tm3(cre)Crm/Sox9^+ Tg(tetO-Vegfa)1Kesh/0	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ	MGI:3840959
cn19	Sox9^tm4.1Tlu/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL	MGI:5293349
cn20	Egfr^tm1Dwt/Egfr^tm1Dwt Sox9^tm3(cre)Crm/Sox9^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd	MGI:6241557
cn21	Gt(ROSA)26Sor^tm1(CAG-Lmx1b,ALPP)Rjo/Gt(ROSA)26Sor^+ Sox9^tm3(cre)Crm/Sox9^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6	MGI:4441200
cn22	Lmx1b^tm1Rjo/Lmx1b^tm1Zfc Sox9^tm3(cre)Crm/Sox9^+	involves: 129S7/SvEvBrd	MGI:4441202
cn23	Gt(ROSA)26Sor^tm6Dym/? Smo^tm2Amc/Smo^tm2Amc Sox9^tm3(cre)Crm/Sox9^+	involves: 129S7/SvEvBrd * 129X1/SvJ	MGI:4366499
cn24	Sox9^tm2Crm/Sox9^+ Rr80^em1Jwsk/Rr80^+ E2f1^Tg(Wnt1-cre)2Sor/E2f1^+	involves: 129S7/SvEvBrd * C3H * C57BL/6J * FVB/NJ	MGI:6720292
cn25	Sox9^tm2Crm/Sox9^+ Tg(Nr5a1-cre)5Asc/?	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3719090
cn26	Sox9^tm2Crm/Sox9^+ H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3718125
cn27	Sox9^tm2Crm/Sox9^+ Tg(Prrx1-cre)1Cjt/0	involves: 129S7/SvEvBrd * C57BL/6J * SJL/J	MGI:2451172
cn28	Sox9^tm3(cre)Crm/Sox9^+ Sp7^tm1Crm/Sp7^tm2Crm	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3610909
cn29	Sox9^tm2Crm/Sox9^+ Tg(Col2a1-cre)1Bhr/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:2451169
cn30	Gnai2^tm2.1Lbi/Gnai2^+ Gnai3^tm1Lbi/Gnai3^tm1Lbi Sox9^tm3(cre)Crm/Sox9^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6	MGI:5471659
cn31	Gnai2^tm2.1Lbi/Gnai2^tm2.1Lbi Gnai3^tm1Lbi/Gnai3^tm1Lbi Sox9^tm3(cre)Crm/Sox9^+	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6	MGI:5471658
cn32	Sox10^tm1Ngan/Sox10^+ Sox9^tm2Crm/Sox9^+ Tg(Rr141-cre)1Ksec/0	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:7451336
cn33	Sox9^tm2Crm/Sox9^+ Tg(Rr141-cre)1Ksec/0	involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:7451331
cn34	Sox10^tm1Ngan/Sox10^+ Sox9^tm1.1Ksec/Sox9^+ Tg(Rr141-cre)1Ksec/0	involves: 129S/SvEv * C57BL/6 * CBA	MGI:7451340
cn35	Sox9^tm1.1Ksec/Sox9^+ Tg(Rr141-cre)1Ksec/0	involves: 129S/SvEv * C57BL/6 * CBA	MGI:7451326
cn36	Ctnnb1^tm1.1Smoc/Ctnnb1^tm1.1Smoc Sox9^em1(cre/ERT2)Tchn/Sox9^+	involves: C57BL/6	MGI:7491703
cn37	Sox9^em1(cre/ERT2)Smoc/Sox9^+ Tnfsf18^em1Pwan/Tnfsf18^em1Pwan	involves: C57BL/6J	MGI:7621581
cn38	Sox9^em1(cre/ERT2)Tchn/Sox9^+ Stk26^tm2.1Zzh/Stk26^tm2.1Zzh	involves: C57BL/6 * SJL	MGI:7491702
cx39	Sox8^tm1Weg/Sox8^tm1Weg Sox9^tm2.1Crm/Sox9^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/6J	MGI:3719087
cx40	Col2a1^tm1(SOX9)Crm/Col2a1^+ Sox9^tm1Crm/Sox9^+	involves: 129S4/SvJae	MGI:3045418

Genotype
MGI:4947115

ht1

• Allelic Composition: Sox9^{tm1(cre/ERT2)Haak}/Sox9⁺
• Genetic Background: B6.129S7-Sox9^{tm1(cre/ERT2)Haak}

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

normal phenotype

no abnormal phenotype detected ( J:166624 )

• mice are viable and fertile, develop normally, and are not smaller than wildtype littermates

Genotype
MGI:5659902

ht2

• Allelic Composition: Sox9^Bbfc/Sox9⁺
• Genetic Background: C57BL/6J-Sox9^Bbfc/GrsrJ

adipose tissue

decreased total body fat amount ( J:223062 )

♂ • much lower total body fat in males but no significant difference in females

decreased percent body fat/body weight ( J:223062 )

♂

vision/eye

vision/eye phenotype ( J:223062 )

N • no abnormalities detected in the eyes

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:223062 )

N • no hearing deficit detected

reproductive system

reproductive system phenotype ( J:223062 )

N • no intersex or putatively sex-reversed mice have been noted, sex ratios are normal at birth, and males are fertile

craniofacial

decreased cranium length ( J:223062 )

short maxilla ( J:223062 )

♂

domed cranium ( J:223062 )

short snout ( J:223062 )

abnormal head shape ( J:223062 )

• both females and males have a shortened snout, reduced skull length, and the skull hight to length ratio is increased consistent with the domed appearance of the head

shortened head ( J:223062 )

growth/size/body

short snout ( J:223062 )

abnormal head shape ( J:223062 )

• both females and males have a shortened snout, reduced skull length, and the skull hight to length ratio is increased consistent with the domed appearance of the head

shortened head ( J:223062 )

decreased body weight ( J:223062 )

♂ • males but not females have a significant decrease in total body mass

skeleton

decreased cranium length ( J:223062 )

short maxilla ( J:223062 )

♂

domed cranium ( J:223062 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:223062

Genotype
MGI:3581014

ht3

• Allelic Composition: Sox9^tm1.1Gsr/Sox9⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:75124 )

• die shortly after birth due to respiratory failure caused by cleft palate

craniofacial

cleft secondary palate ( J:75124 )

skeleton

abnormal humerus morphology ( J:75124 )

absent deltoid tuberosity ( J:75124 )

• deltoid tuberosity of the humerus is missing

scapular bone hypoplasia ( J:75124 )

• hypoplastic and malformed scapula

abnormal skeleton development ( J:75124 )

• exhibit bone malformations typically observed in campomelic dysplasia patients

abnormal bone mineralization ( J:75124 )

• premature mineralization occurs in many skeletal elements, including the tail vertebrae

limbs/digits/tail

abnormal humerus morphology ( J:75124 )

absent deltoid tuberosity ( J:75124 )

• deltoid tuberosity of the humerus is missing

digestive/alimentary system

cleft secondary palate ( J:75124 )

growth/size/body

cleft secondary palate ( J:75124 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:75124

Genotype
MGI:5293346

ht4

• Allelic Composition: Sox9^tm4Tlu/Sox9⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

preweaning lethality, complete penetrance ( J:176950 )

• Background Sensitivity: no heterozygous mice are recovered from either of two chimeric males mated to C57BL/6J females unlike when CD-1 females are used

Genotype
MGI:5293347

ht5

• Allelic Composition: Sox9^tm4Tlu/Sox9⁺
• Genetic Background: involves: 129S4/SvJae * CD-1

mortality/aging

mortality/aging ( J:176950 )

N • Background Sensitivity: mice are recovered when chimeric males are mated to CD-1 females unlike when C57BL/6J females are used

Genotype
MGI:3817222

ht6

• Allelic Composition: Sox9^tm1.1Gsr/Sox9⁺
• Genetic Background: involves: 129S4/SvJae * CD-1

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:141017 )

N • despite islet cell hypoplasia, pancreas size, weight and morphology are normal at E18.5

decreased PP cell number ( J:141017 )

• the number of polypeptide producing cells are reduced

decreased pancreatic alpha cell mass ( J:141017 )

• at E18.5, alpha cell mass is reduced 76% compared to in wild-type mice

decreased pancreatic beta cell mass ( J:141017 )

• at E18.5, beta cell mass is reduced 53% compared to in wild-type mice

decreased pancreatic delta cell number ( J:141017 )

• delta cell numbers are decreased compared to in wild-type mice

pancreatic islet hyperplasia ( J:141017 )

• mice exhibit islet hyperplasia

digestive/alimentary system

digestive/alimentary phenotype ( J:141017 )

N • despite islet cell hypoplasia, pancreas size, weight and morphology are normal at E18.5

Genotype
MGI:3044095

ht7

• Allelic Composition: Sox9^tm1Crm/Sox9⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CD-1

Skeletal malformations of Sox9^tm1Crm/Sox9⁺ mice

mortality/aging

neonatal lethality, complete penetrance ( J:69875 )

• lethal by 20 hours after birth

• delayed or defective precartilagenous condensations observed at E18, result in lethal defects at birth, especially cleft palate

craniofacial

abnormal Meckel's cartilage morphology ( J:69875 )

• Meckel's cartilage is interrupted and bent toward the body midline at E14.5

abnormal hyoid bone morphology ( J:69875 )

• hyoid bone is thinner and bent in the center with the central part of the bone missing in severely affected mutants

short mandible ( J:69875 )

micrognathia ( J:69875 )

cleft secondary palate ( J:69875 )

• bilateral cleft of the secondary palate at birth

bilateral cleft palate ( J:69875 )

bifurcated tongue ( J:69875 )

• bifurcated tongue

skeleton

abnormal Meckel's cartilage morphology ( J:69875 )

• Meckel's cartilage is interrupted and bent toward the body midline at E14.5

abnormal hyoid bone morphology ( J:69875 )

• hyoid bone is thinner and bent in the center with the central part of the bone missing in severely affected mutants

short mandible ( J:69875 )

micrognathia ( J:69875 )

abnormal laryngeal cartilage morphology ( J:69875 )

• thinner laryngeal cartilage

abnormal tracheal cartilage morphology ( J:69875 )

• tracheal rings are thinner

abnormal long bone morphology ( J:69875 )

• variable degrees of bilateral and anterior bending of long bones

absent deltoid tuberosity ( J:69875 )

bowed radius ( J:69875 )

• prominent by E14.5 and occurs in the middle of the bone shaft

bowed ulna ( J:69875 )

• prominent by E14.5; bending is most severe in the ulnae

• angulation of the ulnae is more anterior in the bone shaft than in the radii

bowed tibia ( J:69875 )

• prominent by E14.5

abnormal scapula morphology ( J:69875 )

• the blades of scapulae consist of two parts that are not completely connected at E14.5

abnormal scapular spine morphology ( J:69875 )

• only the two ends of the spines are present, with the major central part missing at E14.5

small scapula ( J:69875 )

• at E18.5

abnormal sternum morphology ( J:69875 )

• manubrium sternum is missing or exhibits anterior bending

abnormal sternebra morphology ( J:69875 )

• sternebrae are thinner and not as regular as in wildtype in neonates

abnormal xiphoid process morphology ( J:69875 )

• xyphoid process is abnormal with a much smaller xiphoid cartilage

short sternum ( J:69875 )

abnormal ilium morphology ( J:69875 )

• ilium is thinner

• ilium is angulated in severely affected mutants

abnormal ischium morphology ( J:69875 )

• ischium is thin

abnormal pubis morphology ( J:69875 )

• bending of the pubic bone in severely affected mutants

small pubis ( J:69875 )

• smaller and thinner

small thoracic cage ( J:69875 )

abnormal skeleton development ( J:69875 )

• all endochondral skeletal elements of E14.5 mutants are smaller and thinner

abnormal cartilage development ( J:69875 )

• cartilage hypoplasia; involves nearly all skeletal elements derived from endochondral ossifications

• development of cartilage primordia is delayed and smaller in size at E12.5

• abnormal bending of cartilage elements observed at E14.5

increased width of hypertrophic chondrocyte zone ( J:69875 )

• hypertrophic zone is larger

abnormal bone mineralization ( J:69875 )

• premature mineralization occurs in many bones, especially the vertebrae and craniofacial bones

digestive/alimentary system

cleft secondary palate ( J:69875 )

• bilateral cleft of the secondary palate at birth

bilateral cleft palate ( J:69875 )

bifurcated tongue ( J:69875 )

• bifurcated tongue

meteorism ( J:69875 )

• heterozygous mutants accumulate air in their stomachs and intestines

limbs/digits/tail

absent deltoid tuberosity ( J:69875 )

bowed radius ( J:69875 )

• prominent by E14.5 and occurs in the middle of the bone shaft

bowed ulna ( J:69875 )

• prominent by E14.5; bending is most severe in the ulnae

• angulation of the ulnae is more anterior in the bone shaft than in the radii

bowed tibia ( J:69875 )

• prominent by E14.5

abnormal tail morphology ( J:69875 )

• frequently exhibit a crooked tail

respiratory system

abnormal laryngeal cartilage morphology ( J:69875 )

• thinner laryngeal cartilage

abnormal tracheal cartilage morphology ( J:69875 )

• tracheal rings are thinner

respiratory distress ( J:69875 )

• heterozygous mutants display gasping respiration and accumulate air in their stomachs and intestines

growth/size/body

cleft secondary palate ( J:69875 )

• bilateral cleft of the secondary palate at birth

bilateral cleft palate ( J:69875 )

bifurcated tongue ( J:69875 )

• bifurcated tongue

meteorism ( J:69875 )

• heterozygous mutants accumulate air in their stomachs and intestines

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:69875

Genotype
MGI:7451325

ht8

• Allelic Composition: Sox9^tm1.2Ksec/Sox9⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * FVB/N

behavior/neurological

impaired swimming ( J:332093 )

circling ( J:332093 )

hearing/vestibular/ear

abnormal endolymphatic duct morphology ( J:332093 )

• reduced proportions of mitochondrial-rich and ribosomal-rich mature cells and concomitant increase immature cells in endolymphatic sac in E14.5 embryos

limbs/digits/tail

kinked tail ( J:332093 )

mortality/aging

perinatal lethality ( J:332093 )

• only ~10% of mice survive

skeleton

chondrodystrophy ( J:332093 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:332093

Genotype
MGI:6241552

cn9

• Allelic Composition: Adam17^tm1.2Bbl/Adam17^tm1.2Bbl; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: B6.129(SJL)-Sox9^tm3(cre)Crm Adam17^tm1.2Bbl

integument

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

dermatitis ( J:229771 )

• dry skin progresses to eczematous lesion (eczematous dermatitis)

• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• about 20% of Vgamma5^neg gammadelta TCR^mid T cells express Vgamma4, but the majority do not

• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5^neg gammadelta TCR^mid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal

• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation

abnormal skin morphology ( J:229771 )

• mice exhibit altered skin microbiota, with a striking overgrowth of S. aureus which is seen within stratum corneum and follicular openings

• skin microbiota undergoes a sequential change where dysbiosis starts with the emergence of Corynebacterium mastitidis and then S. aureus and Corynebacterium bovis predominating later

• antibiotic-treated mice exhibit a higher bacterial diversity, with a reduction in S. aureus and C. bovis, however, withdrawal of antibiotics leads to skin microbiome dysbiosis

• mice treated with antibiotics at 10 weeks after birth show reversal of skin microbiome dysbiosis

abnormal epidermal layer morphology ( J:229771 )

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• antibiotic treatment normalizes epidermal gammadelta T cell constituents

• antibiotic treatment does not affect CD4+ T cell numbers in the epidermis and they remain high, however these T cells produce less IL-4 and do not produce IL-17A or IL-22

dry skin ( J:229771 )

• mice exhibit dry skin around 3 weeks after birth

increased pruritus ( J:229771 )

• mice develop intense pruritus

immune system

increased T-helper 1 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells

increased T-helper 17 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells

• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes

increased T-helper 2 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells

• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes

increased IgE level ( J:229771 )

• serum IgE levels are elevated

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations

abnormal circulating chemokine level ( J:229771 )

• CCL17, a T helper 2 cell chemokine, levels are elevated

dermatitis ( J:229771 )

• dry skin progresses to eczematous lesion (eczematous dermatitis)

• skin lesions show mononuclear cell infiltrates including lymphocytes and mast cells

• epidermal T cell composition is altered, with dendritic epidermal T cells, a resident Vgamma5+ gammadelta T cell subset in epidermis, replaced by massive infiltration of Vgamma5^neg gammadelta TCR^mid T cells and CD4+ T cells

• about 20% of Vgamma5^neg gammadelta TCR^mid T cells express Vgamma4, but the majority do not

• analysis of infiltrating T cells shows that epidermal CD4 T cells consist of Th17 and Th22 cells, and the majority of Vgamma5^neg gammadelta TCR^mid T cells produce interleukin-17 (gammadeltaT17) and a fraction of which also produce interleukin-22

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning are almost completely protected from developing eczematous lesions, however skin inflammation develops upon antibiotic withdrawal

• mice treated with antibiotics at 10 weeks after birth show improvement in eczematous dermatitis and inflammation

hematopoietic system

increased T-helper 1 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th1 cells

increased T-helper 17 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates a prominent increase in Th17 cells

• antibiotic treated mice show a reduction in the numbers of Th17 cells in skin draining lymph nodes

increased T-helper 2 cell number ( J:229771 )

• cytokine expression analysis in skin draining lymph nodes indicates an increase in numbers of Th2 cells

• antibiotic treated mice show a reduction in the numbers of Th2 cells in skin draining lymph nodes

increased IgE level ( J:229771 )

• serum IgE levels are elevated

• mice treated with the antibiotics cefazolin and enrofloxacin after weaning have lower serum IgE concentrations

homeostasis/metabolism

abnormal circulating chemokine level ( J:229771 )

• CCL17, a T helper 2 cell chemokine, levels are elevated

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:229771

Genotype
MGI:5560998

cn10

• Allelic Composition: Sox9^tm3.1Tlu/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: either: (involves: 129S4/SvJae * C57BL/6 * SJL) or (involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL)

behavior/neurological

hunched posture ( J:207801 )

growth/size/body

decreased body height ( J:207801 )

Genotype
MGI:4355046

cn11

• Allelic Composition: Adam17^tm1.2Bbl/Adam17^tm1.2Bbl; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

mortality/aging

premature death ( J:144795 )

• some animals die by 5 months of age, but the majority survive past 5 months

growth/size/body

decreased body weight ( J:144795 )

• after 12 weeks of age, body weight of animals is decreased compared to controls

postnatal growth retardation ( J:144795 )

• mice show retarded growth

enlarged spleen ( J:144795 )

• spleen is proportionately larger by 8 weeks

hematopoietic system

extramedullary hematopoiesis ( J:144795 )

• hematopoiesis occurs in spleen (resulting is splenomegaly) and liver (which becomes more prominent with age)

increased bone marrow cell number ( J:144795 )

• marrow is hypercellular

decreased hematocrit ( J:144795 )

• at 8 weeks

increased hemoglobin content ( J:144795 )

• at 8 weeks

thrombocytosis ( J:144795 )

• at 8 weeks

decreased lymphocyte cell number ( J:144795 )

• white blood cell number is decreased compared to controls at 8 weeks

decreased B cell number ( J:144795 )

• relative decrease compared to controls is observed at 8 weeks

decreased T cell number ( J:144795 )

• relative decrease compared to controls is observed at 8 weeks

increased leukocyte cell number ( J:144795 )

• at 8 weeks

increased neutrophil cell number ( J:144795 )

• increased compared to controls

increased macrophage cell number ( J:144795 )

• increased compared to controls

abnormal spleen morphology ( J:144795 )

• lymphoid follicle development is retarded in 3 week-old mice; at 8 weeks, lymphoid follicles have developed to comparable extent as controls

enlarged spleen ( J:144795 )

• spleen is proportionately larger by 8 weeks

increased spleen red pulp amount ( J:144795 )

• by 8 weeks, expansion of spleen red pulp amount leads to splenomegaly

immune system

decreased lymphocyte cell number ( J:144795 )

• white blood cell number is decreased compared to controls at 8 weeks

decreased B cell number ( J:144795 )

• relative decrease compared to controls is observed at 8 weeks

decreased T cell number ( J:144795 )

• relative decrease compared to controls is observed at 8 weeks

increased leukocyte cell number ( J:144795 )

• at 8 weeks

increased neutrophil cell number ( J:144795 )

• increased compared to controls

increased macrophage cell number ( J:144795 )

• increased compared to controls

abnormal spleen morphology ( J:144795 )

• lymphoid follicle development is retarded in 3 week-old mice; at 8 weeks, lymphoid follicles have developed to comparable extent as controls

enlarged spleen ( J:144795 )

• spleen is proportionately larger by 8 weeks

increased spleen red pulp amount ( J:144795 )

• by 8 weeks, expansion of spleen red pulp amount leads to splenomegaly

increased circulating interleukin-17 level ( J:144795 )

• serum Il17 is significantly elevated

increased interleukin-17 secretion ( J:144795 )

• levels of Il17 are highly elevated compared to controls due to increase in Il17 producing cells

homeostasis/metabolism

increased circulating interleukin-17 level ( J:144795 )

• serum Il17 is significantly elevated

reproductive system

female infertility ( J:144795 )

♀ • females are sterile

reduced male fertility ( J:144795 )

♂ • male fertility is severely impaired

limbs/digits/tail

short femur ( J:144795 )

• femur length is 10-15% shorter than controls

skeleton

abnormal long bone epiphyseal plate proliferative zone ( J:144795 )

• zone is shorter than in controls

abnormal long bone hypertrophic chondrocyte zone ( J:144795 )

• zone is elongated; elongation is prominent at 2-3 weeks of age, and is less evident in older animals

decreased length of long bones ( J:144795 )

• bones are shorter than in controls

short femur ( J:144795 )

• femur length is 10-15% shorter than controls

abnormal bone marrow cavity morphology ( J:144795 )

• metatarsi remained filled with bone marrow cells at least up to 4 months postnatal, whereas bone marrow in control bones is replaced by adipose tissue beginning around 3 weeks of age, and is completely filled with fat cells by 8 weeks after birth

decreased compact bone thickness ( J:144795 )

• beginning at 8 weeks, animals have less cortical bone

decreased trabecular bone thickness ( J:144795 )

• beginning at 8 weeks, animals have less trabecular bone

decreased bone mass ( J:144795 )

• bone mass of femur is decreased compared to controls

osteoporosis ( J:144795 )

• animals show high-turnover type osteoporosis (characterized by increased osteoclast and osteoblast activities by about 8 weeks of age)

abnormal bone remodeling ( J:144795 )

• osteoclast-related (eroded surfaces, osteoclast numbers, and osteoclast surfaces) and osteoblast-related (osteoid volume, osteoid surfaces, and osteoblast surfaces) parameters are increased compared to controls

vision/eye

early eyelid opening ( J:144795 )

• mice are born with their eyes open

integument

abnormal hair growth ( J:144795 )

• mice have hair defects

abnormal skin condition ( J:144795 )

• mice show skin defects

Genotype
MGI:6241555

cn12

• Allelic Composition: Adam17^tm1.2Bbl/Adam17^tm1.2Bbl; Il17a^tm1Yiw/Il17a^tm1Yiw; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * SJL

immune system

dermatitis ( J:229771 )

• mice develop eczematous dermatitis

integument

dermatitis ( J:229771 )

• mice develop eczematous dermatitis

Genotype
MGI:6241556

cn13

• Allelic Composition: Adam17^tm1.2Bbl/Adam17^tm1.2Bbl; Il23a^tm1Dnax/Il23a^tm1Dnax; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * SJL

immune system

dermatitis ( J:229771 )

• mice develop eczematous dermatitis

integument

dermatitis ( J:229771 )

• mice develop eczematous dermatitis

Genotype
MGI:7491701

cn14

• Allelic Composition: Sox9^{em1(cre/ERT2)Tchn}/Sox9⁺; Stk26^tm2.1Zzh/Stk26^tm2.1Zzh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

cellular

abnormal enterocyte proliferation ( J:322311 )

• reduced number of intestinal stem cells and proliferation of intestinal cells

digestive/alimentary system

abnormal enterocyte proliferation ( J:322311 )

• reduced number of intestinal stem cells and proliferation of intestinal cells

homeostasis/metabolism

decreased incidence of tumors by chemical induction ( J:322311 )

• reduced number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas

neoplasm

decreased incidence of tumors by chemical induction ( J:322311 )

• reduced number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas

Genotype
MGI:3817221

cn15

• Allelic Composition: Sox9^tm1Gsr/Sox9⁺; Tg(Pdx1-cre)6Cvw/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA * FVB/N

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:141017 )

N • despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5

decreased PP cell number ( J:141017 )

• at E18.5, the numbers of polypeptide producing cells are reduced compared to wild-type mice

decreased pancreatic alpha cell mass ( J:141017 )

• at E18.5, alpha cell mass is reduced 55% compared to in wild-type mice

decreased pancreatic beta cell mass ( J:141017 )

• at E18.5, beta cell mass is reduced 57% compared to in wild-type mice

• however, beta cell differentiation is normal

decreased pancreatic delta cell number ( J:141017 )

• at E18.5, delta cell numbers are decreased compared to in wild-type mice

pancreatic islet hyperplasia ( J:141017 )

• mice exhibit islet hyperplasia

abnormal pancreas development ( J:141017 )

• the number of pancreatic endocrine progenitor cells is 2-fold less than in wild-type mice due to decreased cell proliferation of endocrine progenitor cells

• however, exocrine progenitor cells are normal in number and proliferation

decreased glucagon secretion ( J:141017 )

• pancreatic glucagons is reduced 34.9% compared to in wild-type

decreased insulin secretion ( J:141017 )

• pancreatic insulin production is decreased 44% compared to in wild-type mice

digestive/alimentary system

digestive/alimentary phenotype ( J:141017 )

N • despite islet cell hypoplasia, pancreas size, weight, morphology and pancreatic exocrine differentiation are normal at E18.5

homeostasis/metabolism

decreased glucagon secretion ( J:141017 )

• pancreatic glucagons is reduced 34.9% compared to in wild-type

decreased insulin secretion ( J:141017 )

• pancreatic insulin production is decreased 44% compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:141017

Genotype
MGI:4849537

cn16

• Allelic Composition: Sox9^tm1Gsr/Sox9⁺; Tg(Pax3-cre)1Joe/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * NMRI * SJL

renal/urinary system

hydroureter ( J:166547 )

• bilateral in 4% of mice at E18.5

• unilateral in 25% of mice at E18.5

distended urinary bladder ( J:166547 )

• in 5% of mice t E18.5

Genotype
MGI:3710216

cn17

• Allelic Composition: Sox9^tm1Gsr/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

cardiovascular system

abnormal heart valve morphology ( J:121352 )

• 75% of mutants, starting at 3 months of age, show mineral deposits in atrioventricular and outflow tract heart valve leaflets compared to 37.5% of controls

abnormal atrioventricular valve morphology ( J:121352 )

• the atrioventricular valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets

calcified mitral valve ( J:121352 )

• adult mitral valves show calcium deposits

abnormal semilunar valve morphology ( J:121352 )

• the outflow tract valve leaflet area is greater than in controls and is associated with an increase in proteoglycans at the tip of the valve leaflets

thick heart valve cusps ( J:121352 )

• from 3 months of age, heart valve leaflets are thickened

Genotype
MGI:3840959

cn18

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Sox9^tm3(cre)Crm/Sox9⁺; Tg(tetO-Vegfa)1Kesh/0
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ

cardiovascular system

abnormal blood vessel morphology ( J:147285 )

• the vascular network of the limbs is denser and more complex

• metacarpal centers are enriched for thicker vessels originating from the axial artery

• metacarpal centers are wider and split into a denser and more complex network of small capillaries in the interdigital areas

• however, formation of avascular areas is not affected

increased vascular endothelial cell number ( J:147285 )

Genotype
MGI:5293349

cn19

• Allelic Composition: Sox9^tm4.1Tlu/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CD-1 * SJL

skeleton

skeleton phenotype ( J:176950 )

N • forelimbs are unaffected

abnormal vertebrae development ( J:176950 )

• intermediate premature ossification at E17.5 in the vertebra

• however, the lumbar vertebra exhibit normal ossification

premature endochondral bone ossification ( J:176950 )

• intermediate at E17.5 in the vertebra

• however, the lumbar vertebra exhibit normal ossification

behavior/neurological

hunched posture ( J:176950 )

growth/size/body

decreased body size ( J:176950 )

Genotype
MGI:6241557

cn20

• Allelic Composition: Egfr^tm1Dwt/Egfr^tm1Dwt; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd

integument

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

dermatitis ( J:229771 )

• mice exhibit eczematous inflammation

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes and Th17, Th22, and Tgammadelta17 inflammation in skin

abnormal skin morphology ( J:229771 )

• mice exhibit skin microbiome dysbiosis, showing increased Corynebacterium spp and S. aureus colonization

abnormal epidermal layer morphology ( J:229771 )

• increase in IL-22 producing epidermal T cells

immune system

increased T-helper 1 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased T-helper 17 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased T-helper 2 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased IgE level ( J:229771 )

• elevation in serum IgE concentrations

dermatitis ( J:229771 )

• mice exhibit eczematous inflammation

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes and Th17, Th22, and Tgammadelta17 inflammation in skin

hematopoietic system

increased T-helper 1 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased T-helper 17 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased T-helper 2 cell number ( J:229771 )

• mice exhibit mixed Th1, Th2, and Th17 cell accumulations in lymph nodes

increased IgE level ( J:229771 )

• elevation in serum IgE concentrations

homeostasis/metabolism

impaired skin barrier function ( J:229771 )

• increase in transepidermal water loss indicating barrier dysfunction

Genotype
MGI:4441200

cn21

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Lmx1b,ALPP)Rjo}/Gt(ROSA)26Sor⁺; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

skeleton

abnormal skeleton morphology ( J:158676 )

• tendon elements exhibit a partial ventral to dorsal conversion with ventral cartilaginous protrusions unlike in wild-type mice

abnormal ankle joint morphology ( J:158676 )

• the ventral flexure at the ankle is absent

abnormal tendon morphology ( J:158676 )

• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice

• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice

• the flexor digitorium sublimus is flattened unlike in wild-type mice

muscle

decreased skeletal muscle mass ( J:158676 )

• mice exhibit loss of muscle tissue in the ventral limb unlike wild-type mice

abnormal tendon morphology ( J:158676 )

• tendon elements exhibit a partial ventral to dorsal conversion with partial conversion of ventral tendon to a dorsal morphology unlike in wild-type mice

• the lateral flexor digitorium profundus tendon is absent unlike in wild-type mice

• the flexor digitorium sublimus is flattened unlike in wild-type mice

limbs/digits/tail

abnormal foot pad morphology ( J:158676 )

• mice exhibit hair on the ventral skin of the paw unlike in wild-type mice

abnormal ankle joint morphology ( J:158676 )

• the ventral flexure at the ankle is absent

Genotype
MGI:4441202

cn22

• Allelic Composition: Lmx1b^tm1Rjo/Lmx1b^tm1Zfc; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S7/SvEvBrd

skeleton

skeleton phenotype ( J:158676 )

N • mice exhibit normal dorsal tendons of the metacarpophalangeal joint

abnormal metacarpal bone morphology ( J:158676 )

• mice exhibit partial duplication of sesamoid bones at the metacarpophalangeal joint compared with wild-type mice

• mice exhibit abnormal tips of the metacarpals

limbs/digits/tail

abnormal metacarpal bone morphology ( J:158676 )

• mice exhibit partial duplication of sesamoid bones at the metacarpophalangeal joint compared with wild-type mice

• mice exhibit abnormal tips of the metacarpals

Genotype
MGI:4366499

cn23

• Allelic Composition: Gt(ROSA)26Sor^tm6Dym/?; Smo^tm2Amc/Smo^tm2Amc; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S7/SvEvBrd * 129X1/SvJ

skeleton

small mandibular condyloid process ( J:153743 )

• at E17.5, the temporomandibular condyle is much smaller in size with loss of growth plate organization unlike in wild-type mice

abnormal temporomandibular joint morphology ( J:153743 )

• the temporomandibular joint forms in close proximity to the condyle resulting in an absence of the lower joint cavity unlike in wild-type mice

craniofacial

small mandibular condyloid process ( J:153743 )

• at E17.5, the temporomandibular condyle is much smaller in size with loss of growth plate organization unlike in wild-type mice

abnormal temporomandibular joint morphology ( J:153743 )

• the temporomandibular joint forms in close proximity to the condyle resulting in an absence of the lower joint cavity unlike in wild-type mice

Genotype
MGI:6720292

cn24

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Rr80^em1Jwsk/Rr80⁺; E2f1^{Tg(Wnt1-cre)2Sor}/E2f1⁺
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6J * FVB/NJ

craniofacial

abnormal mandible morphology ( J:306395 )

• exacerbated compared with wild-type enhancer cluster 1.45

mandibular condyloid process hypoplasia ( J:306395 )

short mandible ( J:306395 )

growth/size/body

postnatal growth retardation ( J:306395 )

skeleton

abnormal mandible morphology ( J:306395 )

• exacerbated compared with wild-type enhancer cluster 1.45

mandibular condyloid process hypoplasia ( J:306395 )

short mandible ( J:306395 )

Genotype
MGI:3719090

cn25

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Tg(Nr5a1-cre)5Asc/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

mortality/aging

neonatal lethality, incomplete penetrance ( J:89368 )

• a small proportion of mice die soon after birth

growth/size/body

disproportionate dwarf ( J:89368 )

• a small proportion of mice have campomelic dysplasia (a form of short-limbed dwarfism)

Genotype
MGI:3718125

cn26

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

craniofacial

abnormal craniofacial morphology ( J:84790 )

• mildly hypoplastic craniofacial skeleton

cleft secondary palate ( J:84790 )

• small cleft secondary palate

digestive/alimentary system

cleft secondary palate ( J:84790 )

• small cleft secondary palate

growth/size/body

cleft secondary palate ( J:84790 )

• small cleft secondary palate

Genotype
MGI:2451172

cn27

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * SJL/J

skeleton

bowed radius ( J:79879 )

• bending of bone

bowed ulna ( J:79879 )

• bending of bone

bowed fibula ( J:79879 )

• bending of bone

bowed tibia ( J:79879 )

• bending of bone

scapular bone hypoplasia ( J:79879 )

abnormal pelvic girdle bone morphology ( J:79879 )

• hypoplasia of pelvic bones

limbs/digits/tail

bowed radius ( J:79879 )

• bending of bone

bowed ulna ( J:79879 )

• bending of bone

bowed fibula ( J:79879 )

• bending of bone

bowed tibia ( J:79879 )

• bending of bone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:79879

Genotype
MGI:3610909

cn28

• Allelic Composition: Sox9^tm3(cre)Crm/Sox9⁺; Sp7^tm1Crm/Sp7^tm2Crm
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:102495 )

• die in the immediate postnatal period due to the absence of bones

skeleton

abnormal limb bone morphology ( J:102495 )

• limb skeletons are hypoplastic, bent, and often deformed

abnormal axial skeleton morphology ( J:102495 )

abnormal rib morphology ( J:102495 )

• ribs are bent and deformed

abnormal vertebrae morphology ( J:102495 )

• vertebrae are bent and deformed

abnormal trabecular bone morphology ( J:102495 )

• endochondral skeletal elements such as the humerus have no bone trabeculae or bone collars

abnormal skeleton development ( J:102495 )

abnormal osteoblast differentiation ( J:102495 )

• osteoblast differentiation is arrested

abnormal bone ossification ( J:102495 )

• exhibit a decrease in endochondral and intramembranous ossification

• skeletal elements formed by endochondral bone formation, including the ribs, limb skeletons, and vertebrae are hypoplastic, bent, and often deformed

abnormal bone mineralization ( J:102495 )

• virtually no mineralization in any facial and skull bones generated by intramembranous bone formation, although very small parts of the maxilla, mandible, and parietal bones were calcified

limbs/digits/tail

abnormal limb bone morphology ( J:102495 )

• limb skeletons are hypoplastic, bent, and often deformed

cellular

abnormal osteoblast differentiation ( J:102495 )

• osteoblast differentiation is arrested

Genotype
MGI:2451169

cn29

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:79879 )

• 95% of animals die 10 days after birth; only a few survive and are able to mate

growth/size/body

disproportionate dwarf ( J:79879 )

skeleton

kyphosis ( J:79879 )

abnormal vertebrae morphology ( J:79879 )

• compression of cervical and thoracic verterbrae

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
campomelic dysplasia		DOID:0050463	OMIM:114290	J:79879

Genotype
MGI:5471659

cn30

• Allelic Composition: Gnai2^tm2.1Lbi/Gnai2⁺; Gnai3^tm1Lbi/Gnai3^tm1Lbi; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6

skeleton

rib fusion ( J:193170 )

• rib fusions are more severe compared to mice homozygous for Gnai3^tm1Lbi alone

Genotype
MGI:5471658

cn31

• Allelic Composition: Gnai2^tm2.1Lbi/Gnai2^tm2.1Lbi; Gnai3^tm1Lbi/Gnai3^tm1Lbi; Sox9^tm3(cre)Crm/Sox9⁺
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6

Rib fusion phenotype is enhanced in Gnai3^tm1Lbi/Gnai3^tm1Lbi mice by loss of Gnai2 in cartilage

skeleton

rib fusion ( J:193170 )

• rib fusions are more severe compared to mice homozygous for Gnai3^tm1Lbi alone

lumbar vertebral fusion ( J:193170 )

• not noticeably more severe than in mice homozygous for Gnai3^tm1Lbi alone

Genotype
MGI:7451336

cn32

• Allelic Composition: Sox10^tm1Ngan/Sox10⁺; Sox9^tm2Crm/Sox9⁺; Tg(Rr141-cre)1Ksec/0
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * CBA

hearing/vestibular/ear

dilated cochlea ( J:332093 )

• larger cross-section of basal cochlear lumen in E15.5 embryos

Genotype
MGI:7451331

cn33

• Allelic Composition: Sox9^tm2Crm/Sox9⁺; Tg(Rr141-cre)1Ksec/0
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6 * CBA

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:332093 )

N • normal cross-section of basal cochlear lumen in E15.5 embryos

Genotype
MGI:7451340

cn34

• Allelic Composition: Sox10^tm1Ngan/Sox10⁺; Sox9^tm1.1Ksec/Sox9⁺; Tg(Rr141-cre)1Ksec/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CBA

hearing/vestibular/ear

dilated cochlea ( J:332093 )

• ~2.7x larger cross-section of basal cochlear lumen in E15.5 embryos

Genotype
MGI:7451326

cn35

• Allelic Composition: Sox9^tm1.1Ksec/Sox9⁺; Tg(Rr141-cre)1Ksec/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * CBA

behavior/neurological

impaired righting response ( J:332093 )

• impaired contact righting starting before weaning

abnormal placing response ( J:332093 )

• onset before weaning

head tilt ( J:332093 )

• onset before weaning

head tossing ( J:332093 )

• onset before weaning

positive geotaxis ( J:332093 )

hyperactivity ( J:332093 )

• onset before weaning

circling ( J:332093 )

• onset before weaning

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:332093 )

N • normal otic vesicles in E9.5embryos

N • normal scala vestibuli morphology in adult mice

N • normal hair cell and stereocilia arrangement in organ of Corti at age P4

N • normal apoptosis rates of cochlea epithelial cells in E14.5 e

dilated cochlea ( J:332093 )

• ~3.2x larger cross-section of basal cochlear lumen in E15.5 embryos

dilated scala media ( J:332093 )

• doubled in size in adult mice

• dilation of cochlear duct starting in E15 em

small scala tympani ( J:332093 )

• ~30% smaller in adult mice

dilated endolymphatic duct ( J:332093 )

• in adult mice and E16.5 embryos

abnormal otolith morphology ( J:332093 )

• at age P9

decreased endocochlear potential ( J:332093 )

• in mature mice

nonsyndromic hearing impairment ( J:332093 )

• hearing deficit from 40 to 80 dB starting before weaning

Genotype
MGI:7491703

cn36

• Allelic Composition: Ctnnb1^tm1.1Smoc/Ctnnb1^tm1.1Smoc; Sox9^{em1(cre/ERT2)Tchn}/Sox9⁺
• Genetic Background: involves: C57BL/6

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:322311 )

• increased number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas and more aggressive progression of colorectal carcinogenesis

neoplasm

increased incidence of tumors by chemical induction ( J:322311 )

• increased number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas and more aggressive progression of colorectal carcinogenesis

Genotype
MGI:7621581

cn37

• Allelic Composition: Sox9^{em1(cre/ERT2)Smoc}/Sox9⁺; Tnfsf18^em1Pwan/Tnfsf18^em1Pwan
• Genetic Background: involves: C57BL/6J

homeostasis/metabolism

decreased circulating alanine transaminase level ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show reduced serum levels of alanine transaminase, indicating reduced liver injury compared to controls

decreased circulating aspartate transaminase level ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show reduced serum levels of aspartate aminotransferase, indicating reduced liver injury compared to controls

abnormal response to injury ( J:346395 )

♂ • mice injected with tamoxifen at 8 weeks of age, followed by a 2 weeks of tamoxifen washout, and then fed a choline-deficient diet supplemented with ethionine (CDE) to induce liver injury (activates liver progenitor cells by transiently inhibiting hepatocyte proliferation) exhibit attenuated ductular reaction, liver inflammation, and liver fibrosis

immune system

decreased CD8-positive, alpha-beta T cell number ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show a reduction in the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumor necrosis factor receptor (GITR)-positive CD8+ T lymphocytes

abnormal T cell activation ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show no increase in GITR+ proportion of CD45+CD3+ T lymphocytes after a 9 week CDE diet, indicating lowered numbers of activated CD45+CD3+ T lymphocytes

decreased inflammatory response ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show attenuated liver inflammation, with reduced liver-infiltrating CD8+ T lymphocytes, no increase in the proportion of activated CD45+CD83+ T lymphocytes, no reduction in the proportion of CD4+ T lymphocytes, and reduced immune cells around the portal area at 9 weeks after CDE injury

liver/biliary system

decreased hepatoblast number ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show reduced proportion of GITRL+Sox9+ and EpCAM+Sox9+ liver progenitor cells among the CD45- liver nonparenchymal cells

hematopoietic system

decreased CD8-positive, alpha-beta T cell number ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show a reduction in the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumor necrosis factor receptor (GITR)-positive CD8+ T lymphocytes

abnormal T cell activation ( J:346395 )

♂ • mice injected with tamoxifen and fed the CDE-diet show no increase in GITR+ proportion of CD45+CD3+ T lymphocytes after a 9 week CDE diet, indicating lowered numbers of activated CD45+CD3+ T lymphocytes

Genotype
MGI:7491702

cn38

• Allelic Composition: Sox9^{em1(cre/ERT2)Tchn}/Sox9⁺; Stk26^tm2.1Zzh/Stk26^tm2.1Zzh
• Genetic Background: involves: C57BL/6 * SJL

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:322311 )

• increased number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas and more aggressive progression of colorectal carcinogenesis

neoplasm

increased incidence of tumors by chemical induction ( J:322311 )

• increased number of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal adenocarcinomas and more aggressive progression of colorectal carcinogenesis

Genotype
MGI:3719087

cx39

• Allelic Composition: Sox8^tm1Weg/Sox8^tm1Weg; Sox9^tm2.1Crm/Sox9⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * C57BL/6J

reproductive system

abnormal seminiferous tubule morphology ( J:89368 )

• at E15.5, male mice have fewer seminiferous tubules

abnormal primary sex determination ( J:89368 )

• 3 of 3 mice exhibit abnormal sex chord development and a clearly outlined coelomic vessel

sex reversal ( J:89368 )

• at E15.5, male mice have areas resembling an ovary

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:89368 )

• at E15.5, male mice have fewer seminiferous tubules

Genotype
MGI:3045418

cx40

• Allelic Composition: Col2a1^tm1(SOX9)Crm/Col2a1⁺; Sox9^tm1Crm/Sox9⁺
• Genetic Background: involves: 129S4/SvJae

mortality/aging

neonatal lethality, incomplete penetrance ( J:90567 )

• 70% die immediately after birth

growth/size/body

decreased body size ( J:90567 )

• 30% of heterozygotes are viable and fertile but very small by 14 days of age

skeleton

abnormal skeleton development ( J:90567 )

• mild hypoplasia of skeletal elements but normal palate and no distortions in long bones, scapula, pelvis, or rib cage