Phenotypes associated with this allele

• Allele Symbol: Racgap1^tm1Mahi
• Allele Name: targeted mutation 1, Masaki Hikida
• Allele ID: MGI:3803293
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Racgap1^tm1Mahi/Racgap1^tm1Mahi Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * CBA	MGI:3804500
cn2	Racgap1^tm1Mahi/Racgap1^tm1Mahi Tg(Stra8-icre)1Reb/0	involves: C57BL/6 * FVB/NJ	MGI:6864268

Genotype
MGI:3804500

cn1

• Allelic Composition: Racgap1^tm1Mahi/Racgap1^tm1Mahi; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * CBA

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

mortality/aging

premature death ( J:137760 )

• mice die 15 - 21 days after poly IC treatment

hematopoietic system

abnormal definitive hematopoiesis ( J:137760 )

• the number of cells in the hematopoietic stem cell fraction is dramatically reduced in poly IC treated mice

abnormal B cell differentiation ( J:137760 )

• bone marrow cells from poly IC treated mice have a reduced capacity to form B-cell progenitors

• cultured B cells trated with IFNG and IL7 to stimulate cre-mediated recombination show about a 70% decrease in the percentage of dividing cells and a 3-fold increase in cells containing 4N DNA

decreased transitional stage B cell number ( J:137760 )

• decrease in the number and percentage of pre-B to mature-B cells in the bone marrow by 14 days after poly IC treatment

decreased pro-B cell number ( J:137760 )

• decrease in the number and percentage of pro-B cells in the bone marrow by 14 days after poly IC treatment

abnormal myelopoiesis ( J:137760 )

• decrease in the number and percentage of the bone marrow myeloid subset by 14 days after poly IC treatment

• bone marrow cells from poly IC treated mice form only a few colonies in all types of myeloid colonies

decreased bone marrow cell number ( J:137760 )

• significant reduction in the total number of bone marrow cells by 14 days after poly IC treatment

abnormal erythrocyte morphology ( J:137760 )

• increase in the percentage of Ter119+CD71^lo erythroid cells in the bone marrow by 14 days after poly IC treatment

immune system

abnormal B cell differentiation ( J:137760 )

• bone marrow cells from poly IC treated mice have a reduced capacity to form B-cell progenitors

• cultured B cells trated with IFNG and IL7 to stimulate cre-mediated recombination show about a 70% decrease in the percentage of dividing cells and a 3-fold increase in cells containing 4N DNA

decreased transitional stage B cell number ( J:137760 )

• decrease in the number and percentage of pre-B to mature-B cells in the bone marrow by 14 days after poly IC treatment

decreased pro-B cell number ( J:137760 )

• decrease in the number and percentage of pro-B cells in the bone marrow by 14 days after poly IC treatment

abnormal myelopoiesis ( J:137760 )

• decrease in the number and percentage of the bone marrow myeloid subset by 14 days after poly IC treatment

• bone marrow cells from poly IC treated mice form only a few colonies in all types of myeloid colonies

Genotype
MGI:6864268

cn2

• Allelic Composition: Racgap1^tm1Mahi/Racgap1^tm1Mahi; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: C57BL/6 * FVB/NJ

reproductive system

abnormal spermatogonia morphology ( J:206583 )

♂ • massive reduction in PLZF-positive undifferentiated spermatogonia pool, starting from 6 dpp

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

decreased male germ cell number ( J:206583 )

♂ • severe decrease in differentiated spermatogonia and primary spermatocytes, with massive reduction in PLZF-positive undifferentiated spermatogonia at 12 dpp

♂ • depletion of germ cell lineage with presence of multinucleated germ cells in pre-pubertal testes at 6, 8, 10 and 12 dpp

azoospermia ( J:206583 )

♂ • no spermatozoa are present in the epididymis or testes

multinucleated giant male germ cells ( J:206583 )

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

♂ • TEM confirmed presence of several syncytial spermatogonia at 10 dpp

♂ • however, all nuclei are properly individualized, indicating normal karyokinesis

abnormal spermatogonia proliferation ( J:206583 )

♂ • marked reduction in Ki67-positive cells at 12 dpp, indicating a division defect of spermatogonial cells that results in multi-nucleated cells and further proliferation arrest

abnormal seminiferous tubule morphology ( J:206583 )

♂ • at 45 dpp, ~91.5% of seminiferous tubules are abnormal with numerous large vacuoles and either (i) lack a germ cell layer, (ii) exhibit a single type of spermatocytes or spermatids, or (iii) contain only Sertoli cells and spermatogonia

abnormal Sertoli cell morphology ( J:206583 )

♂ • at 45 dpp, all testes show large Sertoli cell vacuolization

seminiferous tubule degeneration ( J:206583 )

♂ • at 45 dpp, many seminiferous tubules are markedly atrophic with a decreased number of spermatocytes, spermatids and spermatozoa

small testis ( J:206583 )

♂ • drastic reduction in testis size, starting from 10 to 12 dpp

decreased testis weight ( J:206583 )

♂ • at 45 dpp, mean testes weight is 21.1 mg relative to 68.3 mg in control males

abnormal testis physiology ( J:206583 )

♂ • number of TUNEL-positive cells is significantly reduced in pre-pubertal testes at 10 and 12 dpp

arrest of spermatogenesis ( J:206583 )

♂ • failure to form permanent intercellular bridges in the germ cell lineage induces a spermatogenesis arrest in the PLZF-positive population of undifferentiated spermatogonia

male infertility ( J:206583 )

♂ • all males are sterile

♂ • however, sexual behavior is normal and vaginal plugs are observed in mated females

cellular

abnormal spermatogonia morphology ( J:206583 )

♂ • massive reduction in PLZF-positive undifferentiated spermatogonia pool, starting from 6 dpp

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

decreased male germ cell number ( J:206583 )

♂ • severe decrease in differentiated spermatogonia and primary spermatocytes, with massive reduction in PLZF-positive undifferentiated spermatogonia at 12 dpp

♂ • depletion of germ cell lineage with presence of multinucleated germ cells in pre-pubertal testes at 6, 8, 10 and 12 dpp

azoospermia ( J:206583 )

♂ • no spermatozoa are present in the epididymis or testes

multinucleated giant male germ cells ( J:206583 )

♂ • presence of several bi-nucleated or multi-nucleated spermatogonia at 6-10 dpp

♂ • TEM confirmed presence of several syncytial spermatogonia at 10 dpp

♂ • however, all nuclei are properly individualized, indicating normal karyokinesis

abnormal spermatogonia proliferation ( J:206583 )

♂ • marked reduction in Ki67-positive cells at 12 dpp, indicating a division defect of spermatogonial cells that results in multi-nucleated cells and further proliferation arrest

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:206583 )

♂ • at 45 dpp, ~91.5% of seminiferous tubules are abnormal with numerous large vacuoles and either (i) lack a germ cell layer, (ii) exhibit a single type of spermatocytes or spermatids, or (iii) contain only Sertoli cells and spermatogonia

abnormal Sertoli cell morphology ( J:206583 )

♂ • at 45 dpp, all testes show large Sertoli cell vacuolization

seminiferous tubule degeneration ( J:206583 )

♂ • at 45 dpp, many seminiferous tubules are markedly atrophic with a decreased number of spermatocytes, spermatids and spermatozoa

small testis ( J:206583 )

♂ • drastic reduction in testis size, starting from 10 to 12 dpp

decreased testis weight ( J:206583 )

♂ • at 45 dpp, mean testes weight is 21.1 mg relative to 68.3 mg in control males

abnormal testis physiology ( J:206583 )

♂ • number of TUNEL-positive cells is significantly reduced in pre-pubertal testes at 10 and 12 dpp