Phenotypes associated with this allele

• Allele Symbol: Kat6a^tm1Avo
• Allele Name: targeted mutation 1, Anne K Voss
• Allele ID: MGI:3626344
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kat6a^tm1Avo/Kat6a^tm1Avo	either: 129 or (involves: 129 * C57BL/6) or (129 * BALB/c * FVB/N)	MGI:4418478
hm2	Kat6a^tm1Avo/Kat6a^tm1Avo	involves: 129/Sv * BALB/c * FVB/N	MGI:3629227
ht3	Kat6a^tm1Avo/Kat6a^+	either: (involves: 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6)	MGI:3629229
ht4	Kat6a^tm1Avo/Kat6a^+	involves: 129 * BALB/c * FVB/N	MGI:3629228
cx5	Kat6a^tm1Avo/Kat6a^+ Tbx1^tm1Bld/Tbx1^+	involves: 129 * 129S7/SvEvBrd * BALB/c * C57BL/6	MGI:5447056
cx6	Kat6a^tm1Avo/Kat6a^tm1Avo Tg(RP23-35B9)33Avo/0	involves: 129 * BALB/c * FVB/N	MGI:5447062

Genotype
MGI:4418478

hm1

• Allelic Composition: Kat6a^tm1Avo/Kat6a^tm1Avo
• Genetic Background: either: 129 or (involves: 129 * C57BL/6) or (129 * BALB/c * FVB/N)

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

skeleton

decreased thoracic vertebrae number ( J:155755 )

• 12 rib-bearing thoracic vertebra as compared to the normal complement of 13

thoracic vertebral transformation ( J:155755 )

• a complete anterior homeotic transformation affecting the second cervical vertebra (C2) to the 13th thoracic vertebra (T13)

• presence of an additional 8th cervical vertebra

• additional cervical vertebra, which is ordinarily the first rib-bearing thoracic vertebra, acquires the morphology of the seventh cervical vertebra

• first lumbar vertebra is the first vertebra correctly specified in the mutants

abnormal cervical vertebrae morphology ( J:155755 )

• extended neck region at birth

• presence of an additional 8th cervical vertebra

• tuberculum anterior is absent

• retinoic acid (RA, 10 mg/g) treatment at E7.25 completely rescues the defect

abnormal cervical atlas morphology ( J:155755 )

• the additional cervical vertebra is most similar to the morphology of the atlas

• the first and the supernumerary atlas shared one common enlarged anterior arch of the atlas

nervous system

abnormal innervation ( J:155755 )

• an additional cervical segment in the nervous system

• the 8th (instead of 7th in wild type) intersegmental nerve is the first that contributed to the innervation of the forelimb in mutant embryos

• the first 5 (instead of 4 in wild type) intersegmental nerves contribute to the hypoglossal nerve

behavior/neurological

hunched posture ( J:155755 )

• hunched posture at birth

Genotype
MGI:3629227

hm2

• Allelic Composition: Kat6a^tm1Avo/Kat6a^tm1Avo
• Genetic Background: involves: 129/Sv * BALB/c * FVB/N

mortality/aging

neonatal lethality, complete penetrance ( J:188772 )

• mice die within the first hour after birth

perinatal lethality, complete penetrance ( J:108453 )

• die at birth

hematopoietic system

abnormal thymus development ( J:108453 )

• severe dysgenesis with poor organization, absence of the medulla, and ectopic cystic structures probably of thymic origin

• frequently only 1 lobe descends

small thymus ( J:108453 , J:188772 )

• about 1/4 the size of wild-type; however, overall body size is similar to wild-type (J:108453)

• absence or hypoplasia of the thymus (J:188772)

thymus hypoplasia ( J:108453 )

• lymphoid cells are reduced to 6.7 +/- 2% of wild-type; however lymphoid progenitors are able to differentiate into double positive T cells

athymia ( J:188772 )

• absence or hypoplasia of the thymus

abnormal erythropoiesis ( J:108453 )

• increase in the CD71^high Ter119^high population in the fetal liver

• a 30% decrease in committed erythroid progenitors in the fetal liver is detected using a colony forming assay

decreased double-negative T cell number ( J:108453 )

• at E18.5, a significant decrease in the proportion of double negative T cells is seen in the thymus

decreased bone marrow cell number ( J:108453 )

• very low cellularity (32 +/- 9% of wild-type) and very few progenitors at E18.5

• the number of progenitors decreases from 36.1 +/- 9.8% of wild-type at E12.5 to 6.8 +/- 2.5% at E18.5

increased nucleated erythrocyte cell number ( J:108453 )

• slight but significant increase in the number of nucleated red cells

abnormal hematopoietic stem cell morphology ( J:188772 )

• mice lack transplantable hematopoietic stem cells

decreased hematopoietic stem cell number ( J:108453 )

• results from colony forming assays indicate that the number of committed progenitors for all hematopoietic cell lineages is reduced in the fetal liver

• the early progenitor/stem cell population in the fetal liver is reduced by about 50% compared to wild-type littermates

• fetal liver cells fail to repopulate hematopoietic cells in irradiated recipients and competition assays indicate that the population of fully functional stem cells in the fetal liver is reduced by over 2000-fold compared to wild-type

• however, hematocrit is normal and all leukocyte lineages are present

absent spleen ( J:108453 )

• at E18.5 the site of the spleen is only identified by a poorly developed vascular network and a slight thickening of the mesentery

• however, hematocrit is normal and all leukocyte lineages are present

cardiovascular system

abnormal fourth pharyngeal arch artery morphology ( J:188772 )

• fails to develop on the left side at E10.5

abnormal pulmonary trunk morphology ( J:188772 )

• 26% of mice exhibit a pulmonary trunk curved to the right side, forming an abnormal right aortic arch and a right descending aorta, unlike in wild-type mice

abnormal aortic arch morphology ( J:108453 , J:188772 )

retroesophageal right subclavian artery ( J:188772 )

interrupted aortic arch, type b ( J:188772 )

abnormal heart morphology ( J:188772 )

• mice exhibit incompletely remodeled great vessel walls that appear dilated in diameter and thin walled compared with wild-type mice

overriding aortic valve ( J:188772 )

atrial septal defect ( J:188772 )

atrioventricular septal defect ( J:188772 )

common ventricle ( J:188772 )

• 95% of mice exhibit lack of separation between the left and right ventricles

ventricular septal defect ( J:188772 )

• varying severity affecting either large parts of the septum or the superior, membranous part of the ventricular septum

hemorrhage ( J:108453 )

• occasional minor bleeding is associated with the thymus

craniofacial

abnormal craniofacial morphology ( J:108453 )

• craniofacial defects are seen at birth

abnormal fourth pharyngeal arch artery morphology ( J:188772 )

• fails to develop on the left side at E10.5

micrognathia ( J:188772 )

cleft palate ( J:108453 , J:188772 )

• cleft bony palate (J:188772)

skeleton

micrognathia ( J:188772 )

abnormal vertebrae morphology ( J:188772 )

homeostasis/metabolism

cyanosis ( J:108453 )

• cyanotic but not anemic at birth

immune system

abnormal thymus development ( J:108453 )

• severe dysgenesis with poor organization, absence of the medulla, and ectopic cystic structures probably of thymic origin

• frequently only 1 lobe descends

small thymus ( J:108453 , J:188772 )

• about 1/4 the size of wild-type; however, overall body size is similar to wild-type (J:108453)

• absence or hypoplasia of the thymus (J:188772)

thymus hypoplasia ( J:108453 )

• lymphoid cells are reduced to 6.7 +/- 2% of wild-type; however lymphoid progenitors are able to differentiate into double positive T cells

athymia ( J:188772 )

• absence or hypoplasia of the thymus

decreased double-negative T cell number ( J:108453 )

• at E18.5, a significant decrease in the proportion of double negative T cells is seen in the thymus

absent spleen ( J:108453 )

• at E18.5 the site of the spleen is only identified by a poorly developed vascular network and a slight thickening of the mesentery

• however, hematocrit is normal and all leukocyte lineages are present

digestive/alimentary system

cleft palate ( J:108453 , J:188772 )

• cleft bony palate (J:188772)

embryo

abnormal fourth pharyngeal arch artery morphology ( J:188772 )

• fails to develop on the left side at E10.5

endocrine/exocrine glands

abnormal thymus development ( J:108453 )

• severe dysgenesis with poor organization, absence of the medulla, and ectopic cystic structures probably of thymic origin

• frequently only 1 lobe descends

small thymus ( J:108453 , J:188772 )

• about 1/4 the size of wild-type; however, overall body size is similar to wild-type (J:108453)

• absence or hypoplasia of the thymus (J:188772)

thymus hypoplasia ( J:108453 )

• lymphoid cells are reduced to 6.7 +/- 2% of wild-type; however lymphoid progenitors are able to differentiate into double positive T cells

athymia ( J:188772 )

• absence or hypoplasia of the thymus

growth/size/body

cleft palate ( J:108453 , J:188772 )

• cleft bony palate (J:188772)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:188772

Genotype
MGI:3629229

ht3

• Allelic Composition: Kat6a^tm1Avo/Kat6a⁺
• Genetic Background: either: (involves: 129S2/SvPas) or (involves: 129S2/SvPas * C57BL/6)

reproductive system

reduced fertility ( J:108453 )

• Background Sensitivity: very low fertility on inbred C57BL/6 or 129/Sv backgrounds compared to wild-type or mutants crossed onto a (FVB x BALB/c)F1 background

Genotype
MGI:3629228

ht4

• Allelic Composition: Kat6a^tm1Avo/Kat6a⁺
• Genetic Background: involves: 129 * BALB/c * FVB/N

reproductive system

reproductive system phenotype ( J:108453 )

N • Background Sensitivity: fertility is reduced on inbred C57BL/6 or 129/Sv backgrounds compared to mice on a (FVB x BALB/c)F1 background

hematopoietic system

small thymus ( J:188772 )

• in mice treated with retinoic acid

abnormal definitive hematopoiesis ( J:108453 )

• intermediate reduction in the early progenitor/stem cell population in the fetal liver compared to wild-type and homozygous littermates

• the ability of fetal liver stem cells to compete with wild-type cells is reduced in competitive reconstitution assays but this reduction is not as severe as in homozygous mice

cardiovascular system

retroesophageal right subclavian artery ( J:188772 )

• in mice treated with retinoic acid

interrupted aortic arch, type b ( J:188772 )

• in mice treated with retinoic acid

transposition of great arteries ( J:188772 )

• in mice treated with retinoic acid

craniofacial

cleft secondary palate ( J:188772 )

• in mice treated with retinoic acid

digestive/alimentary system

cleft secondary palate ( J:188772 )

• in mice treated with retinoic acid

homeostasis/metabolism

abnormal response/metabolism to endogenous compounds ( J:188772 )

• mice treated with retinoic acid exhibit an increase in DiGeorge-like symptoms (cleft secondary palate, hypoplasia of the thymus, abnormal RSA, transposition of the great arteries, and IAA-B) compared with wild-type and control mice

immune system

small thymus ( J:188772 )

• in mice treated with retinoic acid

endocrine/exocrine glands

small thymus ( J:188772 )

• in mice treated with retinoic acid

growth/size/body

cleft secondary palate ( J:188772 )

• in mice treated with retinoic acid

Genotype
MGI:5447056

cx5

• Allelic Composition: Kat6a^tm1Avo/Kat6a⁺; Tbx1^tm1Bld/Tbx1⁺
• Genetic Background: involves: 129 * 129S7/SvEvBrd * BALB/c * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:188772 )

• 80% of expected mice die before weaning

cardiovascular system

abnormal cardiovascular system morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

craniofacial

abnormal craniofacial morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

skeleton

abnormal skeleton morphology ( J:188772 )

• more mice exhibit DiGeorge-like symptoms compared with single heterozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
DiGeorge syndrome		DOID:11198	OMIM:188400	J:188772

Genotype
MGI:5447062

cx6

• Allelic Composition: Kat6a^tm1Avo/Kat6a^tm1Avo; Tg(RP23-35B9)33Avo/0
• Genetic Background: involves: 129 * BALB/c * FVB/N

cardiovascular system

cardiovascular system phenotype ( J:188772 )

N • cardiac septal defects observed in Kat6a^tm1Avo homozygotes are rescued

abnormal aortic arch morphology ( J:188772 )

craniofacial

abnormal palate morphology ( J:188772 )

digestive/alimentary system

abnormal palate morphology ( J:188772 )

growth/size/body

abnormal palate morphology ( J:188772 )