Phenotypes associated with this allele

• Allele Symbol: Meis1^tm2Ngc
• Allele Name: targeted mutation 2, Neal G Copeland
• Allele ID: MGI:5464994
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Meis1^tm2Ngc/Meis1^tm2Ngc Nf1^tm1Fcr/Nf1^+ Tg(Dhh-cre)1Mejr/0	involves: 129 * C57BL/6 * C57BL/6J * FVB/N * SJL	MGI:8402603
cn2	Meis1^tm2Ngc/Meis1^tm2Ngc Tg(Tal1-cre/ERT)42-056Jrg/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J	MGI:5464998
cx3	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Meis1^tm2Ngc/Meis1^tm2Ngc Nf1^tm1Fcr/Nf1^+	involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6J * SJL	MGI:8402590

Genotype
MGI:8402603

cn1

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Meis1^tm2Ngc/Meis1^tm2Ngc; Nf1^tm1Fcr/Nf1⁺; Tg(Dhh-cre)1Mejr/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * FVB/N * SJL

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

mortality/aging

premature death ( J:240370 )

• mice succumb to hematopoietic malignancies, with enlarged liver and/or spleen

neoplasm

decreased sarcoma incidence ( J:240370 )

• fewer malignant peripheral nerve sheath tumors are seen compared to mice that do not have Meis1 deleted in nerve glial cells; these tumors stain positive for Meis1, suggesting that they develop in nerve glial cells that escapade inactivation of Meis1

increased hemolymphoid system tumor incidence ( J:240370 )

• about 66% of mice develop hematopoietic neoplasms

• mice that fail to develop malignant peripheral nerve sheath tumors develop hematopoietic disease as indicated by an increase in liver/spleen size

Genotype
MGI:5464998

cn2

• Allelic Composition: Meis1^tm2Ngc/Meis1^tm2Ngc; Tg(Tal1-cre/ERT)42-056Jrg/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J

hematopoietic system

abnormal bone marrow cell morphology/development ( J:192126 )

• tamoxifen-treated mice exhibit reduction in granulocyte-monocyte progenitor (GMPs) and common myeloid progenitor (CMPs) cells and mild reduction in the total number of megakaryocyte/erythroid progenitor cells (MEP) compared with control mice

• however, tamoxifen-treated mice exhibit normal percentage of differentiated myeloid progenitor cells and erythroid progenitor cells and BFU-E and total number of colonies are rescued by re-expression of Hif1a

decreased common myeloid progenitor cell number ( J:192126 )

• tamoxifen-treated mice exhibit reduced common myeloid progenitors and primitive myeloid progenitors compared with control mice

increased hematopoietic stem cell number ( J:192126 )

• increased frequency in tamoxifen-treated mice

abnormal hematopoietic stem cell physiology ( J:192126 )

• long-term hematopoietic stem cells are less quiescent, prone to proliferation and more apoptotic in tamoxifen-treated mice than in control mice

cellular

oxidative stress ( J:192126 )

• increased reactive oxygen species in the long-term hematopoietic stem cells of tamoxifen-treated mice

• however, treatment with N-acetyl-L-cysteine (NAC) restores reactive oxygen species

Genotype
MGI:8402590

cx3

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Meis1^tm2Ngc/Meis1^tm2Ngc; Nf1^tm1Fcr/Nf1⁺
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6J * SJL

mortality/aging

premature death ( J:240370 )

• mice die by 10 months of age

• mice succumb to hematopoietic malignancies

neoplasm

increased neurofibrosarcoma incidence ( J:240370 )

• malignant peripheral nerve sheath tumors are evident typically at 4-6 months of age on the shoulders, ribs, or limbs, in the vicinity of peripheral nerves

increased hemolymphoid system tumor incidence ( J:240370 )

• mice develop hematopoietic neoplasms, with 44% of mice exhibiting hematopoietic malignancies

• mice succumb to hematopoietic malignancies, with enlarged liver and/or spleen

• hematopoietic malignancies typically occur in 6-8 months old mice

nervous system

increased neurofibrosarcoma incidence ( J:240370 )

• malignant peripheral nerve sheath tumors are evident typically at 4-6 months of age on the shoulders, ribs, or limbs, in the vicinity of peripheral nerves

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:240370