Phenotypes associated with this allele

• Allele Symbol: Kmt2a^tm1Clgr
• Allele Name: targeted mutation 1, Michael A Caligiuri
• Allele ID: MGI:3691062
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kmt2a^tm1Clgr/Kmt2a^tm1Clgr	B6.129-Kmt2a^tm1Clgr	MGI:3691212
ht2	Kmt2a^tm1Clgr/Kmt2a^+	B6.129-Kmt2a^tm1Clgr	MGI:3691228
cx3	Flt3^tm1Dgg/Flt3^+ Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445344
cx4	Flt3^tm1Dgg/Flt3^tm1Dgg Kmt2a^tm1Clgr/Kmt2a^+	involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J	MGI:5445345

Genotype
MGI:3691212

hm1

• Allelic Composition: Kmt2a^tm1Clgr/Kmt2a^tm1Clgr
• Genetic Background: B6.129-Kmt2a^tm1Clgr

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

mortality/aging

perinatal lethality, complete penetrance ( J:115001 )

• no pups present at P1, authors did not look at earlier stages

Genotype
MGI:3691228

ht2

• Allelic Composition: Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: B6.129-Kmt2a^tm1Clgr

Vertebral transformation is seen in Kmt2a^tm1Clgr/Mll1⁺ mice at 20 weeks of age

embryo

abnormal rostral-caudal axis patterning ( J:115001 )

• at E12.5 the boundary of Hoxa9 expression in the paraxial mesoderm is shifted ventrally

abnormal paraxial mesoderm morphology ( J:115001 )

skeleton

decreased rib number ( J:115001 )

• rudimentary or missing thirteenth rib in 70% of mice

vertebral transformation ( J:115001 )

thoracic vertebral transformation ( J:115001 )

• rudimentary or missing thirteenth rib indicates transformation of T13 to L1

sacral vertebral transformation ( J:115001 )

• S1 duplication in 63% of mice, indicative of S2 to S1 transformation

hematopoietic system

abnormal common myeloid progenitor cell morphology ( J:115001 )

• increase in the number of mixed colony forming units (GEMM-CFU) formed by cultured splenocytes

• cell from splenocyte colony forming assays form larger secondary colonies in replating assays and are able to form tertiary and quaternary colonies unlike wild-type cells however, in vivo cell counts in the bone marrow, spleen and blood are similar to wild type

• progenitor cells have a 2-fold increase in BrdU incorporation and a 50% increase in the amount of apoptosis

• progenitor cells are able to survive in culture for more than 4 months compared to less than 18 days for wild-type cells

abnormal myelopoiesis ( J:115001 )

• increase in the number of myeloid colony forming units (GM-CFU) formed by cultured splenocytes

increased erythroid progenitor cell number ( J:115001 )

• increase in the number of erythroid burst forming units (BFU-E) formed by cultured splenocytes

abnormal proerythroblast morphology ( J:115001 )

• 5- to 20-fold increase in the number of Ter119+ erythroid cells in the spleen

neoplasm

neoplasm ( J:115001 )

N • despite changes in hematopoiesis and Hoxa gene expression mice do not develop leukemia

immune system

abnormal myelopoiesis ( J:115001 )

• increase in the number of myeloid colony forming units (GM-CFU) formed by cultured splenocytes

Genotype
MGI:5445344

cx3

• Allelic Composition: Flt3^tm1Dgg/Flt3⁺; Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J

mortality/aging

premature death ( J:189096 )

• median survival of 49 weeks of age compared to 75-94 weeks of age for wild-type and single heterozygotes

neoplasm

increased leukemia incidence ( J:189096 )

• 100% penetrance of acute leukemia at a median age of 49 weeks

• 70% develop acute myeloid leukemia

• 12% develop unclassifiable acute leukemia

• 9% develop B-cell leukemia

• 9% develop biphenotypic leukemia

• loss of Flt3 heterozygosity is seen in leukemias

hematopoietic system

enlarged spleen ( J:189096 )

anemia ( J:189096 )

increased erythroblast number ( J:189096 )

• presence of more than or equal to 20% blasts in blood and blasts in nonhematopoietic organs, including liver and adrenal glands

thrombocytopenia ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

• mutants develop leukocytosis

growth/size/body

enlarged spleen ( J:189096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:189096

Genotype
MGI:5445345

cx4

• Allelic Composition: Flt3^tm1Dgg/Flt3^tm1Dgg; Kmt2a^tm1Clgr/Kmt2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/c * C57BL/6J

mortality/aging

premature death ( J:189096 )

• median survival is 19 weeks of age

neoplasm

increased leukemia incidence ( J:189096 )

• 89% develop acute myeloid leukemia

• 11% develop B-cell leukemia

• disease is more aggressive than in double heterozygous mutants

hematopoietic system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

immune system

enlarged spleen ( J:189096 )

increased leukocyte cell number ( J:189096 )

growth/size/body

enlarged spleen ( J:189096 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:189096