Phenotypes Associated with This Genotype

Genotype
MGI:3629227

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

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

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