Phenotypes associated with this allele

• Allele Symbol: Nkapd1^tm1.1Tak
• Allele Name: targeted mutation 1.1, Junji Takeda
• Allele ID: MGI:7868146
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	\Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak	involves: C57BL/6J	MGI:8205283
ht2	\Nkapd1^tm1.1Tak/\Nkapd1^+	involves: C57BL/6J	MGI:8205284
cn3	\Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak \Gt(ROSA)26Sor^tm1(cre/ERT2)Tyj/\Gt(ROSA)26Sor^+	involves: 129S4/SvJae * C57BL/6 * C57BL/6J	MGI:8205290
cn4	\Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak \Tg(Tek-cre)1Ywa/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:8205289
cn5	\Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak \Commd10^Tg(Vav1-icre)A2Kio/\Commd10^+	involves: C57BL/6J * C57BL/10 * CBA/Ca	MGI:8163685

Genotype
MGI:8205283

hm1

• Allelic Composition: \Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak
• Genetic Background: involves: C57BL/6J

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

normal phenotype

no abnormal phenotype detected ( J:350073 )

• mice are viable and fertile, appear grossly normal, and show normal white blood cell (WBC), red blood cell (RBC), and platelet counts in peripheral blood at 6 weeks of age

Genotype
MGI:8205284

ht2

• Allelic Composition: \Nkapd1^tm1.1Tak/\Nkapd1⁺
• Genetic Background: involves: C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:350073 )

• mice are viable and fertile, appear grossly normal, and show normal white blood cell (WBC), red blood cell (RBC), and platelet counts in peripheral blood at 6 weeks of age

Genotype
MGI:8205290

cn3

• Allelic Composition: \Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak; \Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/\Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J

mortality/aging

premature death ( J:350073 )

postnatal lethality ( J:350073 )

• tamoxifen-treated mice begin to die at approximately P14

growth/size/body

abnormal tongue epithelium morphology ( J:350073 )

• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium

decreased body weight ( J:350073 )

• tamoxifen-treated mice lose weight precipitously after P10

hematopoietic system

abnormal definitive hematopoiesis ( J:350073 )

• bone marrow LSK cells cultured in methylcellulose for 9 days show significantly impaired myeloid-erythroid colony forming capability

• flow cytometric analysis indicates stagnation of erythroid differentiation at the pro-erythroblast level

• in vivo and in vitro transplantation assays show that the intrinsic capacity of hematopoietic cells is impaired in adult mice

decreased bone marrow cell number ( J:350073 )

• tamoxifen-treated mice exhibit severely reduced bone marrow cellularity at P10

decreased erythroid progenitor cell number ( J:350073 )

• flow cytometric profiles show a reduced population of TER119⁺ CD71⁺ erythroid progenitors in fetal livers at E14.5

decreased leukocyte cell number ( J:350073 )

• tamoxifen-treated mice exhibit a significantly decreased WBC count in peripheral blood

decreased lymphocyte cell number ( J:350073 )

• tamoxifen-treated mice develop lymphocytopenia in peripheral blood

increased hematopoietic stem cell number ( J:350073 )

• tamoxifen-treated mice show an increase in the absolute numbers of LSK cells in the bone marrow

increased megakaryocyte-erythroid progenitor cell number ( J:350073 )

• tamoxifen-treated mice show a significant increase in the total number of phenotypic megakaryocyte-erythroid progenitors (MEPs) in the bone marrow

• however, total numbers of common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) are not significantly altered in the bone marrow

immune system

small intestinal inflammation ( J:350073 )

• tamoxifen-treated mice show infiltration of inflammatory cells into the mucosal epithelium of the jejunum

decreased leukocyte cell number ( J:350073 )

• tamoxifen-treated mice exhibit a significantly decreased WBC count in peripheral blood

decreased lymphocyte cell number ( J:350073 )

• tamoxifen-treated mice develop lymphocytopenia in peripheral blood

digestive/alimentary system

abnormal tongue epithelium morphology ( J:350073 )

• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium

abnormal esophageal epithelium morphology ( J:350073 )

• tamoxifen-treated mice show loss of the granular layer in the epithelium of the esophagus

abnormal intestinal mucosa morphology ( J:350073 )

• tamoxifen-treated mice exhibit degeneration of the mucosal epithelium of the jejunum and infiltration with inflammatory cells

small intestinal inflammation ( J:350073 )

• tamoxifen-treated mice show infiltration of inflammatory cells into the mucosal epithelium of the jejunum

integument

epidermal atrophy ( J:350073 )

• tamoxifen-treated mice exhibit epidermal atrophy in skin

craniofacial

abnormal tongue epithelium morphology ( J:350073 )

• tamoxifen-treated mice show loss of the granular layer in the tongue epithelium

Genotype
MGI:8205289

cn4

• Allelic Composition: \Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak; \Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:350073 )

• although embryos exhibit normal size and appearance at E10.5, mice die around E14.5

hematopoietic system

hematopoietic system phenotype ( J:350073 )

N • FACS analysis of the caudal half region containing vitelline artery and umbilical artery or yolk sac of E10.5 embryos shows normal populations of c-Kit⁺ CD31⁺ emerging hematopoietic stem cells (HSCs) and c-Kit⁺ CD31⁺ CD45^- hemogenic endothelial cells

N • 3D analysis of aortic hemopoietic clusters shows no alterations in the number and formation of hemogenic clusters in the dorsal aorta, indicating normal endothelial-to-hematopoietic transition

Genotype
MGI:8163685

cn5

• Allelic Composition: \Nkapd1^tm1.1Tak/\Nkapd1^tm1.1Tak; \Commd10^{Tg(Vav1-icre)A2Kio}/\Commd10⁺
• Genetic Background: involves: C57BL/6J * C57BL/10 * CBA/Ca

mortality/aging

lethality during fetal growth through weaning, complete penetrance ( J:350073 )

• although fetuses are present in expected Mendelian ratios until E14.5, no live pups are born

perinatal lethality, complete penetrance ( J:350073 )

liver/biliary system

small liver ( J:350073 )

• fetal liver atrophy is noted at E14.5

homeostasis/metabolism

subcutaneous edema ( J:350073 )

• fetuses show subcutaneous edema at E16.5

hematopoietic system

abnormal definitive hematopoiesis ( J:350073 )

• at E14.5, fetal liver cells show a decrease in the proportion of acidophilic erythroblasts and denucleated red blood cells (i.e. mature erythroid cells) and an increase in the proportion of pro-erythroblasts and basophilic erythroblasts (i.e. immature erythroid cells) with no apparent dysplasia

• E14.5 fetal liver LSK cells cultured in methylcellulose produce fewer and smaller (< 100 cells) colonies, indicating impaired capacity for myeloid and erythroid development

• limiting dilution analysis of E14.5 FL LSK cells using MS-5 co-culture indicates that none of the LSK cells have hematopoietic growth potential

• in vivo transplantation assays show that LSK cells lack the ability to reconstitute hematopoiesis after transplantation into lethally irradiated mice

abnormal B cell differentiation ( J:350073 )

• E14.5 fetal liver LSK cells co-cultured with the murine stromal cell line MS-5 in the presence of SCF, Flt3-ligand and IL-7 fail to generate CD19+ B cells

anemia ( J:350073 )

• embryos appear grossly normal until E12.5 but become anemic from E14.5

abnormal hematopoietic precursor cell morphology ( J:350073 )

• at E14.5, the proportion of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) is increased, whereas that of lymphoid-primed multipotent progenitors (LMPPs) and common lymphoid progenitors (CLPs) is decreased in fetal livers

• more mature precursors bearing lineage-related markers such as CD11b or TER119 are markedly decreased

• however, the proportion and number of common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), and megakaryocyte-erythroid progenitors (MEPs) is not significantly altered

decreased common lymphocyte progenitor cell number ( J:350073 )

• at E14.5, the proportion of common lymphoid progenitors (CLPs) is decreased in fetal livers

increased hematopoietic stem cell number ( J:350073 )

• at E14.5, fetal liver cells show increased numbers and ratios of Lineage^-Sca-1⁺c-Kit^high (LSK) cells; flow cytometric analysis shows an increased proportion of hematopoietic stem cells (HSCs)

abnormal fetal liver hematopoietic progenitor cell morphology ( J:350073 )

• at E14.5, fetal liver cells show increased numbers and ratios of Lineage^-Sca-1⁺c-Kit^high (LSK) cells, which represent fetal liver hematopoietic stem/progenitor cells (HSPCs)

• fetal liver HSPC differentiation is impaired at early stages in all lineage directions

abnormal erythroid lineage cell morphology ( J:350073 )

• at E14.5, the fetal liver shows a significant reduction in the relative ratio and the absolute number of TER119+ erythroid cells

decreased erythroid progenitor cell number ( J:350073 )

• flow cytometric profiles show a reduced population of TER119^Hi CD71^Hi mature erythroid progenitors in fetal livers at E14.5

abnormal proerythroblast morphology ( J:350073 )

• at E14.5, fetal liver cells show an increase in the proportion of proerythroblasts; flow cytometric profiles show an enlarged proerythroblast (TER119^-/Lo CD71^Hi) population

abnormal erythroblast number ( J:350073 )

• at E14.5, fetal liver cells show a decrease in the proportion of acidophilic erythroblasts and an increase in the proportion of basophilic erythroblasts

cellular

abnormal cell cycle ( J:350073 )

• after a 3- or 5-day culture of fetal liver-derived LSK cells in differentiation medium, the number of cells yielded is significantly lower than in control-derived cells

• after a 5-day culture, the % of cells in the S-G2/M phase is significantly lower than in control-derived cells

increased apoptosis ( J:350073 )

• after a 5-day culture of fetal liver-derived LSK cells in differentiation medium, annexin V staining shows a significant increase in the number of apoptotic cells in both the early and late phases; the % of apoptotic cells (DNA content < 2n) is significantly higher than in control-derived cells

immune system

abnormal B cell differentiation ( J:350073 )

• E14.5 fetal liver LSK cells co-cultured with the murine stromal cell line MS-5 in the presence of SCF, Flt3-ligand and IL-7 fail to generate CD19+ B cells

integument

subcutaneous edema ( J:350073 )

• fetuses show subcutaneous edema at E16.5