Phenotypes associated with this allele

• Allele Symbol: Kdm5a^tm1.1Kael
• Allele Name: targeted mutation 1.1, William G Kaelin
• Allele ID: MGI:3798768
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael	B6.129S6-Rbp2^tm1.1Kael	MGI:3798864
hm2	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL	MGI:3798793
hm3	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael	involves: 129S6/SvEvTac * FVB/N	MGI:5296669
cx4	Kdm5a^tm1.1Kael/Kdm5a^+ Rb1^tm1Tyj/Rb1^+	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296663
cx5	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1^+	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296664
cx6	Kdm5a^tm1.1Kael/Kdm5a^+ Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296665
cx7	Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael Rb1^tm1Tyj/Rb1^tm1Tyj	involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N	MGI:5296668

Genotype
MGI:3798864

hm1

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael
• Genetic Background: B6.129S6-Rbp2^tm1.1Kael

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

mortality/aging

neonatal lethality, complete penetrance ( J:137333 )

• Background Sensitivity: homozygotes on a C57BL/6 congenic background die soon after birth; homozygotes on a mixed 129S6 - C57BL/6 - FVB/N - SJL background are viable

Genotype
MGI:3798793

hm2

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

growth/size/body

decreased body size ( J:137333 )

• mice are 20-30% smaller than wild-type littermates

hematopoietic system

abnormal definitive hematopoiesis ( J:137185 )

• myeloid progenitor compartment consisting of common myeloid progenitors (CMP), granulocyte-monocyte progenitors, and megakaryocyte-erythrocyte progenitors, shows significantly decreased rate of apoptosis relative to wild-type

increased neutrophil cell number ( J:137185 )

• 6- or 23-week old mice exhibit relative (44% vs 58% for wild-type vs null) and absolute neutrophilia in peripheral blood compared to control littermates

abnormal hematopoietic stem cell morphology ( J:137185 )

• HSC compartment shows significantly decreased rate of apoptosis relative to wild-type

cellular

abnormal cell cycle ( J:137185 )

• myeloid and HSC progenitors show abnormalities in cell cycle progression such as increased percentages of G0/1 cells in G1 indicating trend toward increased proportion of progenitor cells entering the S/G2/M phase (increased entry into cell cycle)

behavior/neurological

abnormal behavior ( J:137185 , J:137333 )

abnormal involuntary movement ( J:137333 )

• when mice are suspended by the tail, legs tremble

immune system

increased neutrophil cell number ( J:137185 )

• 6- or 23-week old mice exhibit relative (44% vs 58% for wild-type vs null) and absolute neutrophilia in peripheral blood compared to control littermates

Genotype
MGI:5296669

hm3

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

cellular

early cellular replicative senescence ( J:175625 )

• in mouse embryonic fibroblasts

Genotype
MGI:5296663

cx4

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a⁺; Rb1^tm1Tyj/Rb1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

neoplasm

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 16 of 18 mice

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 16 of 18 mice

nervous system

increased pituitary gland tumor incidence ( J:175625 )

• in 15 of 18 mice; 9 of 12 with intermediate lobe origins, 1 in 12 anterior lobe origins, and 2 of 12 intermediate and anterior lobe origins

Genotype
MGI:5296664

cx5

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael; Rb1^tm1Tyj/Rb1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:175625 )

• median survival is 72 weeks

neoplasm

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

nervous system

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

endocrine/exocrine glands

increased pituitary gland tumor incidence ( J:175625 )

• in 8 of 10 mice; 3 of 4 with intermediate lobe origins and 1 in 4 anterior lobe origins

increased thyroid tumor incidence ( J:175625 )

• in 8 of 10 mice

Genotype
MGI:5296665

cx6

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a⁺; Rb1^tm1Tyj/Rb1^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:175625 )

cellular

increased fibroblast proliferation ( J:175625 )

• in mouse embryonic fibroblasts

Genotype
MGI:5296668

cx7

• Allelic Composition: Kdm5a^tm1.1Kael/Kdm5a^tm1.1Kael; Rb1^tm1Tyj/Rb1^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:175625 )

cellular

cellular phenotype ( J:175625 )

N • embryonic fibroblasts exhibit normal cell proliferation

abnormal cell differentiation ( J:175625 )

• mouse embryonic fibroblasts transfected with a vector expressing Myod1 (MyoD) exhibit reduced differentiate into myocytes unlike similarly treated wild-type cells

• differentiation is enhanced by transfection with the Rb1 variant delta663, which doesn't bind E2F or repress E2F-dependent promoters