Phenotypes associated with this allele

• Allele Symbol: Nkx2-3^tm1Hha
• Allele Name: targeted mutation 1, Hans-Henning Arnold
• Allele ID: MGI:2386680
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nkx2-3^tm1Hha/Nkx2-3^tm1Hha	involves: 129S4/SvJae	MGI:3608330
hm2	Nkx2-3^tm1Hha/Nkx2-3^tm1Hha	involves: 129S4/SvJae * C57BL/6	MGI:3608329

Genotype
MGI:3608330

hm1

• Allelic Composition: Nkx2-3^tm1Hha/Nkx2-3^tm1Hha
• Genetic Background: involves: 129S4/SvJae

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

immune system

abnormal leukocyte migration ( J:62129 )

• homozygotes show severely impaired homing of lymphocytes into the spleen, Peyer's patches and mesenteric lymph nodes, largely due to loss of expression of the mucosal homing receptor Madcam1

decreased lymphocyte cell number ( J:62129 )

• homozygotes exhibit an ~40% reduction in the absolute number of lymphocytes relative to wild-type mice

decreased B cell number ( J:62129 )

• homozygotes show no significant changes of cell composition in blood, bone marrow or peripheral LNs

• however, mutants exhibit a significant shift in the relative ratio of B220⁺ B cells to CD4⁺ and CD8⁺ T cells in favor of T cells in spleen

decreased T cell number ( J:62129 )

• homozygotes exhibit a moderate but significant relative reduction of T cells in mesenteric LNs

abnormal spleen morphology ( J:62129 )

• homozygotes exhibit gross alterations of spleen leukocyte composition and tissue architecture, independent of the genetic background

abnormal marginal zone B cell morphology ( J:62129 )

• specific marginal zone B cells are either completely absent or partially misplaced in mutant spleen

absent marginal zone B cells ( J:62129 )

• marginal zone phenotype B cells (i.e. CD21^high CD23^low B220⁺ cells) are absent in mutant spleens, whereas IgM⁺ IgD^- cells remain relatively unchanged

abnormal metallophilic macrophage morphology ( J:62129 )

• substantially fewer MOMA-1+ macrophages are present in the marginal zone

abnormal spleen marginal zone macrophage morphology ( J:62129 )

• marginal sinus-lining macrophages are either completely absent or partially misplaced in mutant spleen

intermingled spleen red and white pulp ( J:62129 )

• a clear demarcation of red and white pulp is absent

small spleen ( J:62129 )

• Background Sensitivity: occasional asplenia is noted in a mixed genetic background involving 129S4/SvJae and C57BL/6, while a less severe spleen size reduction is observed in 129/Sv inbred mice

decreased spleen weight ( J:62129 )

• 129/Sv inbred homozygotes display a significantly reduced spleen size relative to wild-type mice (mean wet weight is 56 mg vs 85 mg)

abnormal spleen marginal sinus morphology ( J:62129 )

• homozygotes exhibit large interstitial gaps that resemble a dilated marginal sinus containing a disrupted endothelium that fails to separate the red from the white pulp

absent spleen marginal zone ( J:62129 )

• homozygotes fail to form a marginal zone that normally locates between follicles and the red pulp

abnormal spleen periarteriolar lymphoid sheath morphology ( J:62129 )

• homozygotes fail to exhibit an identifiable PALS

decreased spleen white pulp amount ( J:62129 )

• homozygotes exhibit a generally smaller and less branched spleen white pulp containing lymphocytes that are extensively intermingled with erythrocytes at its periphery

abnormal Peyer's patch follicle morphology ( J:62129 )

• homozygotes exhibit significantly reduced PPs with only one or two follicles

decreased Peyer's patch number ( J:62129 )

• homozygotes exhibit only a few identifiable Peyer's patches (PPs) that are significantly smaller than wild-type PPs

• T and B cells are detected in roughly the appropriate position in remaining PPs; however, the proportion of IgD⁺ B cells is reduced

small Peyer's patches ( J:62129 )

abnormal mesenteric lymph node morphology ( J:62129 )

• mutant mesenteric LNs occasionally display an ill-defined follicle structure with T cells partially misplaced into the cortical region

• in contrast, mutant peripheral LNs appear morphologically unremarkable

hematopoietic system

abnormal leukocyte migration ( J:62129 )

• homozygotes show severely impaired homing of lymphocytes into the spleen, Peyer's patches and mesenteric lymph nodes, largely due to loss of expression of the mucosal homing receptor Madcam1

decreased lymphocyte cell number ( J:62129 )

• homozygotes exhibit an ~40% reduction in the absolute number of lymphocytes relative to wild-type mice

decreased B cell number ( J:62129 )

• homozygotes show no significant changes of cell composition in blood, bone marrow or peripheral LNs

• however, mutants exhibit a significant shift in the relative ratio of B220⁺ B cells to CD4⁺ and CD8⁺ T cells in favor of T cells in spleen

decreased T cell number ( J:62129 )

• homozygotes exhibit a moderate but significant relative reduction of T cells in mesenteric LNs

abnormal spleen morphology ( J:62129 )

• homozygotes exhibit gross alterations of spleen leukocyte composition and tissue architecture, independent of the genetic background

abnormal marginal zone B cell morphology ( J:62129 )

• specific marginal zone B cells are either completely absent or partially misplaced in mutant spleen

absent marginal zone B cells ( J:62129 )

• marginal zone phenotype B cells (i.e. CD21^high CD23^low B220⁺ cells) are absent in mutant spleens, whereas IgM⁺ IgD^- cells remain relatively unchanged

abnormal metallophilic macrophage morphology ( J:62129 )

• substantially fewer MOMA-1+ macrophages are present in the marginal zone

abnormal spleen marginal zone macrophage morphology ( J:62129 )

• marginal sinus-lining macrophages are either completely absent or partially misplaced in mutant spleen

intermingled spleen red and white pulp ( J:62129 )

• a clear demarcation of red and white pulp is absent

small spleen ( J:62129 )

• Background Sensitivity: occasional asplenia is noted in a mixed genetic background involving 129S4/SvJae and C57BL/6, while a less severe spleen size reduction is observed in 129/Sv inbred mice

decreased spleen weight ( J:62129 )

• 129/Sv inbred homozygotes display a significantly reduced spleen size relative to wild-type mice (mean wet weight is 56 mg vs 85 mg)

abnormal spleen marginal sinus morphology ( J:62129 )

• homozygotes exhibit large interstitial gaps that resemble a dilated marginal sinus containing a disrupted endothelium that fails to separate the red from the white pulp

absent spleen marginal zone ( J:62129 )

• homozygotes fail to form a marginal zone that normally locates between follicles and the red pulp

abnormal spleen periarteriolar lymphoid sheath morphology ( J:62129 )

• homozygotes fail to exhibit an identifiable PALS

decreased spleen white pulp amount ( J:62129 )

• homozygotes exhibit a generally smaller and less branched spleen white pulp containing lymphocytes that are extensively intermingled with erythrocytes at its periphery

cellular

abnormal leukocyte migration ( J:62129 )

• homozygotes show severely impaired homing of lymphocytes into the spleen, Peyer's patches and mesenteric lymph nodes, largely due to loss of expression of the mucosal homing receptor Madcam1

Genotype
MGI:3608329

hm2

• Allelic Composition: Nkx2-3^tm1Hha/Nkx2-3^tm1Hha
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:54198 )

• Background Sensitivity: experiments on 129/Sv and C57BL/6 inbred backgrounds provide evidence for strain-dependent variability of postnatal lethality

• homozygotes of a mixed genetic background are born alive; however, more than 50% die within 3 weeks after birth, presumably due to digestive malfunctions

digestive/alimentary system

abnormal intestine morphology ( J:54198 )

• at 2 months, adult homozygotes display a significantly enlarged intestinal tract, with a wider gut lumen, prolonged villi and thickened mesenchyme primarily in the jejunum

abnormal intestinal epithelium morphology ( J:54198 )

• at E15 and thereafter, homozygotes show significantly reduced epithelial folding in the jejunum; in addition, the gut mesenchyme is slightly reduced

abnormal crypts of Lieberkuhn morphology ( J:54198 )

• at 2 months, adult homozygotes show a marked expansion and disorganization of the crypt compartment

abnormal small intestine morphology ( J:54198 )

• at 2 months, adult homozygotes display an enlarged small intestine, as a result of larger villi and a thickened mesenchymal layer in the jejunum; disintegration of the lamina propia and increased density of blood vessels is observed

abnormal ileum morphology ( J:54198 )

abnormal jejunum morphology ( J:54198 )

• at E14.5 and thereafter, homozygotes exhibit a delay in villus formation in the jejunum, with significantly fewer villi of reduced size and abnormal bifurcations and branching noted at E17.5; less severe morphological changes are observed in the ileum, while the duodenum and colon remain largely unaffected

hematopoietic system

small spleen ( J:54198 )

• at P3, ~80% of homozygotes exhibit a small spleen

abnormal spleen primary B follicle morphology ( J:54198 )

• adult homozygotes lack the typical follicular structure of wild-type white pulp

• primary follicles lack IgM-positive B cells, which are either completely absent or mislocated

absent spleen marginal zone ( J:54198 )

• adult homozygotes show no clear splenic marginal zone

decreased spleen white pulp amount ( J:54198 )

• in adult homozygotes, the white pulp is reduced in size

abnormal splenic cell ratio ( J:54198 )

• mutant spleens show absence of granulocytes and macrophages, as well as significantly reduced numbers of B and T cells, in the absence of a general hematopoietic defect

absent spleen ( J:54198 )

• >20% of adult homozygotes display absence of spleen

immune system

small spleen ( J:54198 )

• at P3, ~80% of homozygotes exhibit a small spleen

abnormal spleen primary B follicle morphology ( J:54198 )

• adult homozygotes lack the typical follicular structure of wild-type white pulp

• primary follicles lack IgM-positive B cells, which are either completely absent or mislocated

absent spleen marginal zone ( J:54198 )

• adult homozygotes show no clear splenic marginal zone

decreased spleen white pulp amount ( J:54198 )

• in adult homozygotes, the white pulp is reduced in size

abnormal splenic cell ratio ( J:54198 )

• mutant spleens show absence of granulocytes and macrophages, as well as significantly reduced numbers of B and T cells, in the absence of a general hematopoietic defect

absent spleen ( J:54198 )

• >20% of adult homozygotes display absence of spleen

growth/size/body

cachexia ( J:54198 )

• homozygotes become increasingly cachectic

postnatal growth retardation ( J:54198 )

• homozygotes exhibit severe growth retardation; however, survivors of the weaning period gain weight normally, and eventually approach the size of wild-type littermates

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:54198 )

• at 2 months, adult homozygotes show a marked expansion and disorganization of the crypt compartment

cellular

abnormal cell proliferation ( J:54198 )

• at E15 and thereafter, homozygotes show significantly reduced proliferation of intervillus epithelial cells in the jejunum

• in contrast, adult homozygotes exhibit a 2- to 3-fold increase in the proliferation and migration rate of crypt cells along the longitudinal villus axis of the small intestine

• no significant changes in apoptosis in the mutant villus or crypt epithelium are observed

• at E14.5 and thereafter, homozygotes exhibit a delay in villus formation in the jejunum, with significantly fewer villi of reduced size and abnormal bifurcations and branching noted at E17.5; less severe morphological changes are observed in the ileum, while the duodenum and colon remain largely unaffected

cardiovascular system

abnormal blood vessel morphology ( J:54198 )

• at 2 months, adult homozygotes exhibit extensive hypervascularization and reduction of leukocytes in the villus cores of the small intestine