Phenotypes associated with this allele

• Allele Symbol: Gja1^tm8Kwi
• Allele Name: targeted mutation 8, Klaus Willecke
• Allele ID: MGI:3776013
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gja1^tm8Kwi/Gja1^+ Tg(Pgk1-cre)1Lni/0	involves: 129S2/SvPas * BALB/c * C57BL/6	MGI:3807710
cn2	Gja1^tm8Kwi/Gja1^+ Tg(Nes-cre)1Kln/0	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:3807708
cn3	Gja1^tm8Kwi/Gja1^+ Tg(Myh6-cre)2182Mds/0	involves: 129S2/SvPas * FVB/N	MGI:3807709

Genotype
MGI:3807710

cn1

• Allelic Composition: Gja1^tm8Kwi/Gja1⁺; Tg(Pgk1-cre)1Lni/0
• Genetic Background: involves: 129S2/SvPas * BALB/c * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:132032 )

• 54% lethality occurs between E14.5 and 16.5

craniofacial

abnormal craniofacial morphology ( J:132032 )

• only males were tested

• observed in 70% of mutants

abnormal zygomatic arch morphology ( J:132032 )

• mutants have different angle of zygomatic arch relative to wild-type

abnormal tooth hard tissue morphology ( J:132032 )

• decreased enamel thickness in is observed as translucent teeth which wear faster with age

reduced enamel thickness ( J:132032 )

• 80% of mutants display enamel hypoplasia

small mandible ( J:132032 )

• mandible size in mutants is reduced compared to wild-type

abnormal nasal bone morphology ( J:132032 )

• some mice have differences in angle of nasal bone compared to wild-type

small face ( J:132032 )

• some mutants show obvious compactness of facial region

depressed nasal bridge ( J:132032 )

• depressed nasal bridge is seen in some mutants with craniofacial abnormalites

limbs/digits/tail

syndactyly ( J:132032 )

• 70% of mutants exhibit syndactyly (type III); this is observed in second, third, and fourth digits on all limbs

skeleton

abnormal skeleton morphology ( J:132032 )

• bone abnormalities were examined in males only

abnormal zygomatic arch morphology ( J:132032 )

• mutants have different angle of zygomatic arch relative to wild-type

abnormal tooth hard tissue morphology ( J:132032 )

• decreased enamel thickness in is observed as translucent teeth which wear faster with age

reduced enamel thickness ( J:132032 )

• 80% of mutants display enamel hypoplasia

small mandible ( J:132032 )

• mandible size in mutants is reduced compared to wild-type

abnormal nasal bone morphology ( J:132032 )

• some mice have differences in angle of nasal bone compared to wild-type

decreased bone mineral density ( J:132032 )

• osteopenia is observed in mutants

abnormal trabecular bone morphology ( J:132032 )

• trabecular spacing is increased; however, although trabecular thickness is not different, osteoblast number is not decreased significantly

decreased trabecular bone mass ( J:132032 )

• mutants have a reduction in trabecular bone mass

cellular

abnormal cell physiology ( J:132032 )

• cultured cells show 2-fold higher ATP release upon stimulation in calcium-free solution compared to wild-type cells

integument

sparse hair ( J:132032 )

• observed in 30% of mutants and becomes more pronounced with age

growth/size/body

abnormal tooth hard tissue morphology ( J:132032 )

• decreased enamel thickness in is observed as translucent teeth which wear faster with age

reduced enamel thickness ( J:132032 )

• 80% of mutants display enamel hypoplasia

abnormal nasal bone morphology ( J:132032 )

• some mice have differences in angle of nasal bone compared to wild-type

small face ( J:132032 )

• some mutants show obvious compactness of facial region

depressed nasal bridge ( J:132032 )

• depressed nasal bridge is seen in some mutants with craniofacial abnormalites

microcephaly ( J:132032 )

respiratory system

abnormal nasal bone morphology ( J:132032 )

• some mice have differences in angle of nasal bone compared to wild-type

depressed nasal bridge ( J:132032 )

• depressed nasal bridge is seen in some mutants with craniofacial abnormalites

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oculodentodigital dysplasia		DOID:0060291	OMIM:164200 OMIM:257850	J:132032

Genotype
MGI:3807708

cn2

• Allelic Composition: Gja1^tm8Kwi/Gja1⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

mortality/aging

mortality/aging ( J:132032 )

N • deletion of Gja1 in early neurons does not affect survival of mice; number of mutants per litter and average litter size do not differ from expected

Genotype
MGI:3807709

cn3

• Allelic Composition: Gja1^tm8Kwi/Gja1⁺; Tg(Myh6-cre)2182Mds/0
• Genetic Background: involves: 129S2/SvPas * FVB/N

mortality/aging

premature death ( J:132032 )

• mutants are born live die during initial 6.5 months after birth

lethality throughout fetal growth and development, incomplete penetrance ( J:132032 )

• 44% lethality occurs between E14.5 and 16.5

cardiovascular system

cardiovascular system phenotype ( J:132032 )

N • mice do not differ significantly from wild-type in left ventricular (lv) muscle mass, lv end-diastolic volume and lv ejection fraction

N • postnatally, mice do not differ significantly from wild-type in left ventricular (lv) muscle mass, lv end-diastolic volume and lv ejection fraction

ventricular tachycardia ( J:132032 )

• cardiac arrythmias are observed are observed after excorporation for ex vivo cardiac functional analyses including spontaneous and sustained ventricular tachycardias

irregular heartbeat ( J:132032 )

• cardiac arrythmias are observed are observed after excorporation for ex vivo cardiac functional analyses including spontaneous and sustained ventricular tachycardias

• in vivo, spontaneous arrhythmic events such as ventricular extra systole (VES) are observed; frequency and severity of such events increase with by hypoxic stimulation

abnormal heart electrocardiography waveform feature ( J:132032 )

• surface and intercardiac ECGs ex vivo show a broadening of the QRS complex and decrease in the R wave in ventricle activity indicating disturbed impulse propagation

prolonged QRS complex duration ( J:132032 )

abnormal R wave ( J:132032 )

• decrease in the R wave

abnormal myocardial fiber physiology ( J:132032 )

• isolated fetal cardiomyocytes show a 1.6-fold higher beating frequency than wild-type cells