Phenotypes associated with this allele

• Allele Symbol: Jag1^tm2Grid
• Allele Name: targeted mutation 2, Tom Gridley
• Allele ID: MGI:3692444
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Jag1^tm1Grid/Jag1^tm2Grid Foxg1^tm1(cre)Skm/Foxg1^+	involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6	MGI:3693201
cn2	Jag1^tm2Grid/Jag1^tm2Grid H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S1/Sv * C57BL/6 * CBA	MGI:5318528
cn3	Jag1^tm1Grid/Jag1^tm2Grid Tg(Tagln-cre)1Her/0	involves: 129S1/Sv * C57BL/6 * SJL	MGI:4867007
cn4	Jag1^tm2Grid/Jag1^tm2Grid Tg(Tek-cre)12Flv/0	involves: C3H * C57BL/6	MGI:4867008

Genotype
MGI:3693201

cn1

• Allelic Composition: Jag1^tm1Grid/Jag1^tm2Grid; Foxg1^tm1(cre)Skm/Foxg1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * C57BL/6

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

mortality/aging

perinatal lethality, complete penetrance ( J:115783 )

• mutants survive through E18.5

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:115783 )

N • at E15.5, inner ear structures not associated with sensory formation such as endolymphatic duct and sac, and crus are not affected

abnormal cochlea morphology ( J:115783 )

• formation of prosensory domain is disrupted by E18.5

abnormal cochlear hair cell morphology ( J:115783 )

• severe hair cell patterning defects are observed at E18.5

• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches

• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions

• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

absent tunnel of Corti ( J:115783 )

• at E18.5, tunnel of Corti is not apparent

decreased cochlea coiling ( J:115783 )

abnormal lateral semicircular canal morphology ( J:115783 )

• semicircular canals are mostly absent, with only a small portion of lateral semicircular canal present at E15.5

abnormal crista ampullaris morphology ( J:115783 )

• cristae and ampullae are missing or severely disrupted by E14.5 in homozygotes

abnormal superior semicircular canal morphology ( J:115783 )

• at E15.5, only a small portion of the anterior canal is present in homozygotes

absent semicircular canals ( J:115783 )

• at E15.5, semicircular canals are largely absent

abnormal utricular macula morphology ( J:115783 )

• structure is extremely small, with few differentiating hair cells; severe disruption of differentiation of utricular macula is observed

small utricle ( J:115783 )

• observed at E13.5

abnormal vestibular saccule morphology ( J:115783 )

• at E13.5, saccule appears misshapen

• at E18.5, saccule and macula are relatively normal, but entire saccular structure is shaped differently compared to controls

nervous system

abnormal cochlear hair cell morphology ( J:115783 )

• severe hair cell patterning defects are observed at E18.5

• no clear formation of rows or distinction between inner and outer hair cells is observed in midbasal regions of the organ of Corti; hair cells form in patches

• at E16.5, patterns look similar to those at E18.5 with patches of hair cells in midbasal regions and absent hair cells in very basal regions

• in middle portion of cochlea, patterning of inner and sparse outer hair cells is abnormal

abnormal cochlear hair cell number ( J:115783 )

• in apical turn of cochlea, there are only two rows instead of four rows of hair cells

absent cochlear hair cells ( J:115783 )

• no hair cell formation is observed in basal turns of cochlea; at E18.5, hair cells and supporting cells are absent in very basal region of cochlea

abnormal cochlear outer hair cell morphology ( J:115783 )

• no outer hair cells or supporting Deiter's cells are present in apex of cochlea

Genotype
MGI:5318528

cn2

• Allelic Composition: Jag1^tm2Grid/Jag1^tm2Grid; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

mortality/aging

premature death ( J:181120 )

• maxilla deficiencies lead to poor feeding and death around one month of age

growth/size/body

malocclusion ( J:181120 )

• dental occlusion is misaligned with severe midface hypoplasia requiring trimming of the lower incisors weekly

midface hypoplasia ( J:181120 )

• midfacial hypoplasia resulting in a reduction in anterior facial width

abnormal palate morphology ( J:181120 )

• the palatal dimensions are proportionally smaller, however the structural components are in tact

• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium

• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5

• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5

abnormal primary palate development ( J:181120 )

• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected

• mutants exhibit delayed palatal shelf elongation

• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants

decreased palatal length ( J:181120 )

• palate shelf height is reduced in both the anterior and posterior regions

decreased body size ( J:181120 )

craniofacial

malocclusion ( J:181120 )

• dental occlusion is misaligned with severe midface hypoplasia requiring trimming of the lower incisors weekly

short maxilla ( J:181120 )

• shortened maxillary regions; anterior-posterior facial length is normal at P0 but over time the mutants exhibit smaller maxillary lengths

• the inframaxillary length and the posterior-anterior length are reduced

midface hypoplasia ( J:181120 )

• midfacial hypoplasia resulting in a reduction in anterior facial width

abnormal palate morphology ( J:181120 )

• the palatal dimensions are proportionally smaller, however the structural components are in tact

• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium

• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5

• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5

abnormal primary palate development ( J:181120 )

• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected

• mutants exhibit delayed palatal shelf elongation

• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants

decreased palatal length ( J:181120 )

• palate shelf height is reduced in both the anterior and posterior regions

skeleton

malocclusion ( J:181120 )

• dental occlusion is misaligned with severe midface hypoplasia requiring trimming of the lower incisors weekly

short maxilla ( J:181120 )

• shortened maxillary regions; anterior-posterior facial length is normal at P0 but over time the mutants exhibit smaller maxillary lengths

• the inframaxillary length and the posterior-anterior length are reduced

behavior/neurological

abnormal eating behavior ( J:181120 )

• mutants exhibit poor feeding after 30 days of age due to malocclusion and require soft mouse chow

cardiovascular system

abnormal blood vessel morphology ( J:181120 )

• mutants exhibit aberrant vascular pattering in the palate; reduced vascular branching in the palate at E14.5 and E15.5, reduced vasculature organization and vessel size, poor vascular smooth muscle investment, and irregular vessel formation

digestive/alimentary system

abnormal palate morphology ( J:181120 )

• the palatal dimensions are proportionally smaller, however the structural components are in tact

• mutants exhibit reduced proliferation in the palate shelves at E14.5 and in the adjacent palatal epithelium

• mutants exhibit reduced hyaluronic acid in the palate shelves at E14.5

• mutants exhibit aberrant vascular pattering in the palate including reduced vascular branching at E14.5 and E15.5

abnormal primary palate development ( J:181120 )

• at E14.5, palatal shelf elevation above the tongue occurs normally but palatal elongation is reduced anteriorly, whereas the posterior palate shelf length is unaffected

• mutants exhibit delayed palatal shelf elongation

• some E15.5 mutants show delayed palate shelf apposition and the persistence of the epithelial seam, however palate fusion occurs in all mutants

decreased palatal length ( J:181120 )

• palate shelf height is reduced in both the anterior and posterior regions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alagille syndrome		DOID:9245	OMIM:118450 OMIM:610205	J:181120

Genotype
MGI:4867007

cn3

• Allelic Composition: Jag1^tm1Grid/Jag1^tm2Grid; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * SJL

mortality/aging

perinatal lethality, incomplete penetrance ( J:166769 )

• 50% of mutants die by P1

postnatal lethality, complete penetrance ( J:166769 )

• no mutants survive past P2

cardiovascular system

retroesophageal right subclavian artery ( J:166769 )

• seen in some mutants

patent ductus arteriosus ( J:166769 )

• 95% of mutants exhibit patent ductus arteriosus

abnormal vascular smooth muscle morphology ( J:166769 )

• defects in vascular smooth muscle cell differentiation in the outer layers of the medial wall of the ductus arteriosus and descending aorta at E17.5 when the ductus arteriosus is still patent, however the ascending limb of the aorta and the pulmonary artery trunk have normal vascular smooth muscle cell differentiation

homeostasis/metabolism

cyanosis ( J:166769 )

muscle

abnormal vascular smooth muscle morphology ( J:166769 )

• defects in vascular smooth muscle cell differentiation in the outer layers of the medial wall of the ductus arteriosus and descending aorta at E17.5 when the ductus arteriosus is still patent, however the ascending limb of the aorta and the pulmonary artery trunk have normal vascular smooth muscle cell differentiation

cellular

patent ductus arteriosus ( J:166769 )

• 95% of mutants exhibit patent ductus arteriosus

Genotype
MGI:4867008

cn4

• Allelic Composition: Jag1^tm2Grid/Jag1^tm2Grid; Tg(Tek-cre)12Flv/0
• Genetic Background: involves: C3H * C57BL/6

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:166769 )

• die at approximately E10.5

cardiovascular system

abnormal vascular smooth muscle morphology ( J:166769 )

• non-cell autonomous defects in vascular smooth muscle cell differentiation

pericardial edema ( J:166769 )

hemorrhage ( J:166769 )

embryo

abnormal vitelline vascular remodeling ( J:166769 )

• fail to remodel the primary vascular plexus of the yolk sac to form large blood vessels

homeostasis/metabolism

pericardial edema ( J:166769 )

muscle

abnormal vascular smooth muscle morphology ( J:166769 )

• non-cell autonomous defects in vascular smooth muscle cell differentiation