Phenotypes associated with this allele

• Allele Symbol: Alx3^tm1Hubr
• Allele Name: targeted mutation 1, Hubrecht Institute
• Allele ID: MGI:2151910
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Alx3^tm1Hubr/Alx3^tm1Hubr	involves: 129P2/OlaHsd	MGI:5475526
hm2	Alx3^tm1Hubr/Alx3^tm1Hubr	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5489776
hm3	Alx3^tm1Hubr/Alx3^tm1Hubr	involves: 129P2/OlaHsd * FVB/N	MGI:2183234
ht4	Alx3^tm1Hubr/Alx3^+	involves: 129P2/OlaHsd	MGI:5475527
cx5	Alx1^tm1Crm/Alx1^tm1Crm Alx3^tm1Hubr/Alx3^tm1Hubr	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:3769582
cx6	Alx3^tm1Hubr/Alx3^tm1Hubr Alx4^lst-J/Alx4^lst-J	involves: 129P2/OlaHsd * C3H * C57BL/6J * FVB/N	MGI:2173156
cx7	Alx3^tm1Hubr/Alx3^tm1Hubr Alx4^lst-J/Alx4^lst-J	involves: 129P2/OlaHsd * C3HeB/FeJ * C57BL/6J	MGI:3769581

Genotype
MGI:5475526

hm1

• Allelic Composition: Alx3^tm1Hubr/Alx3^tm1Hubr
• Genetic Background: involves: 129P2/OlaHsd

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:166436 )

♂N • serum insulin levels are similar to controls

decreased insulin secretion ( J:166436 )

♂

increased fasting circulating glucose level ( J:166436 )

♂ • elevated fasting blood glucose levels

increased circulating insulin level ( J:166436 )

♂ • about 28% of 36-40 week old mice become hyperinsulinemic after glucose injection

impaired glucose tolerance ( J:166436 )

♂ • impaired at both 12-16 weeks of age and at 36-40 weeks of age

insulin resistance ( J:166436 )

• no impairemnt over all in insulin sensitivity although 28.5% of mice become totally unresponsive to insulin

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:166436 )

♂

small pancreatic islets ( J:166436 )

♂ • islet size is reduced in adults

abnormal pancreatic beta cell physiology ( J:166436 )

♂ • total insulin content of iselts is lower than in controls

increased pancreatic beta cell apoptosis ( J:166436 )

♂ • significantly increased percentage of apoptotic beta cells in 15 week old mice and increased further at 36 weeks

decreased insulin secretion ( J:166436 )

♂

cellular

increased pancreatic beta cell apoptosis ( J:166436 )

♂ • significantly increased percentage of apoptotic beta cells in 15 week old mice and increased further at 36 weeks

Genotype
MGI:5489776

hm2

• Allelic Composition: Alx3^tm1Hubr/Alx3^tm1Hubr
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

preweaning lethality, incomplete penetrance ( J:163651 )

• fewer than expected mice are present after weaning

neonatal lethality, incomplete penetrance ( J:163651 )

• defective mice die shortly after birth

reproductive system

reduced female fertility ( J:163651 )

♀ • in female mice fed a folic acid deficient diet

embryo

embryonic growth retardation ( J:163651 )

• at E9.5, somite number varied between 6 and 22 indicating developmental delay

• in 30 of 37 mice from dams fed a folic acid-free diet

abnormal head mesenchyme morphology ( J:163651 )

• craniofacial mesenchyme is less densely packed with fewer interconnections, increased extracellular space and more abundant clusters of blood cells compared with wild-type mice

abnormal embryonic neuroepithelium morphology ( J:163651 )

• at the 21-somite stage, the inner surface of the neuroepithelium is convex and the edges of the neural folds are pointing towards the outside

open neural tube ( J:163651 )

• in 1 of 6 12-somite mice

• in the cranial neural tube of most mice at the 14-somite stage

• in 30% of mice from dams fed a folic acid-free diet unlike wild-type mice

craniofacial

abnormal craniofacial development ( J:163651 )

• in some mice with increased cell death in the forehead spreading laterally and dorsally

midline facial cleft ( J:163651 )

• in some mice at E18.5

vision/eye

failure of eyelid fusion ( J:163651 )

• at E18.5 in some mice

cellular

abnormal cell death ( J:163651 )

• increased cell death of craniofacial cells in the forehead spreading laterally and dorsally

growth/size/body

midline facial cleft ( J:163651 )

• in some mice at E18.5

embryonic growth retardation ( J:163651 )

• at E9.5, somite number varied between 6 and 22 indicating developmental delay

• in 30 of 37 mice from dams fed a folic acid-free diet

abnormal head mesenchyme morphology ( J:163651 )

• craniofacial mesenchyme is less densely packed with fewer interconnections, increased extracellular space and more abundant clusters of blood cells compared with wild-type mice

nervous system

abnormal embryonic neuroepithelium morphology ( J:163651 )

• at the 21-somite stage, the inner surface of the neuroepithelium is convex and the edges of the neural folds are pointing towards the outside

open neural tube ( J:163651 )

• in 1 of 6 12-somite mice

• in the cranial neural tube of most mice at the 14-somite stage

• in 30% of mice from dams fed a folic acid-free diet unlike wild-type mice

exencephaly ( J:163651 )

• in some mice at E18.5

Genotype
MGI:2183234

hm3

• Allelic Composition: Alx3^tm1Hubr/Alx3^tm1Hubr
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

skeleton

skeleton phenotype ( J:71880 )

N • homozygotes are viable, fertile, and display a normal lifespan in the absence of skeletal abnormalities in newborn mice

Genotype
MGI:5475527

ht4

• Allelic Composition: Alx3^tm1Hubr/Alx3⁺
• Genetic Background: involves: 129P2/OlaHsd

homeostasis/metabolism

increased circulating glucose level ( J:166436 )

♂ • elevated fasting blood glucose levels

impaired glucose tolerance ( J:166436 )

♂ • impaired at both 12-16 weeks of age and at 36-40 weeks of age

Genotype
MGI:3769582

cx5

• Allelic Composition: Alx1^tm1Crm/Alx1^tm1Crm; Alx3^tm1Hubr/Alx3^tm1Hubr
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

skeleton

abnormal scapula morphology ( J:101708 )

• reduction of the anterior part of the scapular blade

Genotype
MGI:2173156

cx6

• Allelic Composition: Alx3^tm1Hubr/Alx3^tm1Hubr; Alx4^lst-J/Alx4^lst-J
• Genetic Background: involves: 129P2/OlaHsd * C3H * C57BL/6J * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:71880 )

• double mutant mice generally die within a few hours after birth

craniofacial

abnormal craniofacial bone morphology ( J:71880 )

• at E12.5 and E13.5, double mutant frontal, parietal, and nasal bones are severely abnormal and reduced

• the alisphenoid and squamosal bones are malformed and reduced

• the basipresphenoid and pterygoid processes are severely deformed and broader

• notably, the posterior elements of the sphenoid bone, the occipital bone and the otic capsule, tympanic ring, inner and middle ear structures appear normal

• these craniofacial defects are first apparent at ~E10.5, when the nasal processes appear to be abnormally positioned

abnormal cranium morphology ( J:71880 )

• at E12.5 and E13.5, double mutants display a broader posterior skull, while the anterior skull is truncated

• most facial bones and many other neural crest derived skull elements are deformed, truncated or even absent

abnormal basicranium morphology ( J:71880 )

• at E12.5 and E13.5, double mutants display a severely deformed and broader skull base

decreased cranium height ( J:71880 )

• double mutants display a short cranium, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

increased cranium width ( J:71880 )

• double mutants display a broad cranium, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

abnormal neurocranium morphology ( J:71880 )

• double mutant newborns display an abnormal skull vault due to a size reduction in the parietal, frontal and nasal bones

large fontanelles ( J:71880 )

• double mutant newborns display wide fontanelles

small parietal bone ( J:71880 )

• double mutants display a more severe size reduction of the parietal bone than single Alx4^lst-J homozygotes

small alisphenoid bone ( J:71880 )

abnormal pterygoid process morphology ( J:71880 )

short temporal bone squamous part ( J:71880 )

abnormal viscerocranium morphology ( J:71880 )

• most facial bones are deformed, truncated or even absent

small frontal bone ( J:71880 )

• double mutants display a more severe size reduction of the frontal bone than single Alx4^lst-J homozygotes

abnormal mandible morphology ( J:71880 )

• at E12.5 and E13.5, the distal part of the dentaries is truncated

• however, incisors are present and the proximal part of the mandible appears normal

abnormal maxilla morphology ( J:71880 )

• at E12.5 and E13.5, the double mutant premaxilla and maxilla are positioned abnormally laterally

abnormal maxillary frontal process morphology ( J:71880 )

• at E10.5, the double mutant nasal processes (frontal processes of maxilla) are spaced more laterally than in wild-type embryos

abnormal premaxilla morphology ( J:71880 )

• at E12.5 and E13.5, the double mutant premaxilla and maxilla are positioned abnormally laterally

small nasal bone ( J:71880 )

• double mutants display a severe size reduction of the nasal bones

absent facial bone ( J:71880 )

short facial bone ( J:71880 )

abnormal nasal capsule morphology ( J:71880 )

• in double mutant mice, the nasal capsule is split into two separate halves closed by remnants of the nasal septum

• at E12.5 and E13.5, the nasal labyrinths and anterior part of the nasal capsule are severely deformed and curved

cleft palate ( J:71880 )

abnormal nasal cavity morphology ( J:71880 )

• at E12.5 and E13.5, double mutant nasal cavities are malformed

• in contrast, more posterior cranial structures, like the palatal processes and tongue, appear normal

absent nasal septum ( J:71880 )

• double mutant newborns lack a medial nasal septum

bifid nasal tip ( J:71880 )

• mildly affected double mutants display only a partially split nasal tip

bifid nose ( J:71880 )

• double mutant newborns display a highly variable split nose, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

• in severe cases, both lateral halves of the nose are anteriorly truncated and spaced wide apart

midline facial cleft ( J:71880 )

• double mutant newborns display a highly variable midfacial clefting of the entire nose region, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

• the earliest anatomical defects leading to the cleft nose phenotype are first detected at E10.5, when the nasal processes grow out abnormally laterally

• as a result, the medial nasal processes fail to fuse in the facial midline at E11.5, causing the split nose phenotype

• these defects are associated with a significant number of mesenchymal cells undergoing apoptosis at E10.0 in a restricted region of the frontonasal process of double mutatnt embryos

limbs/digits/tail

preaxial polydactyly ( J:71880 )

• double mutant mice exhibit preaxial polydactyly of the fore- and hindlimbs, similar to that observed in single Alx4^lst-J homozygotes

absent deltoid tuberosity ( J:71880 )

• double mutants lack the deltoid crests, similar to single Alx4^lst-J homozygotes

skeleton

abnormal craniofacial bone morphology ( J:71880 )

• at E12.5 and E13.5, double mutant frontal, parietal, and nasal bones are severely abnormal and reduced

• the alisphenoid and squamosal bones are malformed and reduced

• the basipresphenoid and pterygoid processes are severely deformed and broader

• notably, the posterior elements of the sphenoid bone, the occipital bone and the otic capsule, tympanic ring, inner and middle ear structures appear normal

• these craniofacial defects are first apparent at ~E10.5, when the nasal processes appear to be abnormally positioned

abnormal cranium morphology ( J:71880 )

• at E12.5 and E13.5, double mutants display a broader posterior skull, while the anterior skull is truncated

• most facial bones and many other neural crest derived skull elements are deformed, truncated or even absent

abnormal basicranium morphology ( J:71880 )

• at E12.5 and E13.5, double mutants display a severely deformed and broader skull base

decreased cranium height ( J:71880 )

• double mutants display a short cranium, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

increased cranium width ( J:71880 )

• double mutants display a broad cranium, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

abnormal neurocranium morphology ( J:71880 )

• double mutant newborns display an abnormal skull vault due to a size reduction in the parietal, frontal and nasal bones

large fontanelles ( J:71880 )

• double mutant newborns display wide fontanelles

small parietal bone ( J:71880 )

• double mutants display a more severe size reduction of the parietal bone than single Alx4^lst-J homozygotes

small alisphenoid bone ( J:71880 )

abnormal pterygoid process morphology ( J:71880 )

short temporal bone squamous part ( J:71880 )

abnormal viscerocranium morphology ( J:71880 )

• most facial bones are deformed, truncated or even absent

small frontal bone ( J:71880 )

• double mutants display a more severe size reduction of the frontal bone than single Alx4^lst-J homozygotes

abnormal mandible morphology ( J:71880 )

• at E12.5 and E13.5, the distal part of the dentaries is truncated

• however, incisors are present and the proximal part of the mandible appears normal

abnormal maxilla morphology ( J:71880 )

• at E12.5 and E13.5, the double mutant premaxilla and maxilla are positioned abnormally laterally

abnormal maxillary frontal process morphology ( J:71880 )

• at E10.5, the double mutant nasal processes (frontal processes of maxilla) are spaced more laterally than in wild-type embryos

abnormal premaxilla morphology ( J:71880 )

• at E12.5 and E13.5, the double mutant premaxilla and maxilla are positioned abnormally laterally

small nasal bone ( J:71880 )

• double mutants display a severe size reduction of the nasal bones

absent facial bone ( J:71880 )

short facial bone ( J:71880 )

abnormal nasal capsule morphology ( J:71880 )

• in double mutant mice, the nasal capsule is split into two separate halves closed by remnants of the nasal septum

• at E12.5 and E13.5, the nasal labyrinths and anterior part of the nasal capsule are severely deformed and curved

absent deltoid tuberosity ( J:71880 )

• double mutants lack the deltoid crests, similar to single Alx4^lst-J homozygotes

abnormal clavicle morphology ( J:71880 )

• double mutants exhibit a reduction of the medial (sternal) end of the clavicle; not observed in single Alx4^lst-J homozygotes

vision/eye

exophthalmos ( J:71880 )

• double mutant newborns display bulging eyes apparently due to cranial defects

eyelids open at birth ( J:71880 )

• double mutant newborns display wide open eyes more often than single Alx4^lst-J homozygotes

behavior/neurological

absent gastric milk in neonates ( J:71880 )

• double mutant newborns contain no milk in their stomachs

growth/size/body

small nasal bone ( J:71880 )

• double mutants display a severe size reduction of the nasal bones

abnormal nasal capsule morphology ( J:71880 )

• in double mutant mice, the nasal capsule is split into two separate halves closed by remnants of the nasal septum

• at E12.5 and E13.5, the nasal labyrinths and anterior part of the nasal capsule are severely deformed and curved

cleft palate ( J:71880 )

abnormal nasal cavity morphology ( J:71880 )

• at E12.5 and E13.5, double mutant nasal cavities are malformed

• in contrast, more posterior cranial structures, like the palatal processes and tongue, appear normal

absent nasal septum ( J:71880 )

• double mutant newborns lack a medial nasal septum

bifid nasal tip ( J:71880 )

• mildly affected double mutants display only a partially split nasal tip

bifid nose ( J:71880 )

• double mutant newborns display a highly variable split nose, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

• in severe cases, both lateral halves of the nose are anteriorly truncated and spaced wide apart

midline facial cleft ( J:71880 )

• double mutant newborns display a highly variable midfacial clefting of the entire nose region, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

• the earliest anatomical defects leading to the cleft nose phenotype are first detected at E10.5, when the nasal processes grow out abnormally laterally

• as a result, the medial nasal processes fail to fuse in the facial midline at E11.5, causing the split nose phenotype

• these defects are associated with a significant number of mesenchymal cells undergoing apoptosis at E10.0 in a restricted region of the frontonasal process of double mutatnt embryos

meteorism ( J:71880 )

• double mutant newborns display air-distended intestines

respiratory system

small nasal bone ( J:71880 )

• double mutants display a severe size reduction of the nasal bones

abnormal nasal capsule morphology ( J:71880 )

• in double mutant mice, the nasal capsule is split into two separate halves closed by remnants of the nasal septum

• at E12.5 and E13.5, the nasal labyrinths and anterior part of the nasal capsule are severely deformed and curved

abnormal nasal cavity morphology ( J:71880 )

• at E12.5 and E13.5, double mutant nasal cavities are malformed

• in contrast, more posterior cranial structures, like the palatal processes and tongue, appear normal

absent nasal septum ( J:71880 )

• double mutant newborns lack a medial nasal septum

bifid nasal tip ( J:71880 )

• mildly affected double mutants display only a partially split nasal tip

bifid nose ( J:71880 )

• double mutant newborns display a highly variable split nose, similar to mice that are homozygous for Alx3^tm1Fme and heterozygous for Alx4^lst-J, and mice that are heterozygous for Alx3^tm1Fme and homozygous for Alx4^lst-J

• in severe cases, both lateral halves of the nose are anteriorly truncated and spaced wide apart

digestive/alimentary system

cleft palate ( J:71880 )

meteorism ( J:71880 )

• double mutant newborns display air-distended intestines

Genotype
MGI:3769581

cx7

• Allelic Composition: Alx3^tm1Hubr/Alx3^tm1Hubr; Alx4^lst-J/Alx4^lst-J
• Genetic Background: involves: 129P2/OlaHsd * C3HeB/FeJ * C57BL/6J

skeleton

small pubis ( J:101708 )