Phenotypes associated with this allele

• Allele Symbol: Arid4b^tm1Alb
• Allele Name: targeted mutation 1, Arthur L Beaudet
• Allele ID: MGI:3687005
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arid4b^tm1Alb/Arid4b^tm1Alb	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717485
ht2	Arid4b^tm1Alb/Arid4b^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717486
cn3	Arid4b^tm1Alb/Arid4b^tm1.1Mywu Tg(Amh-cre)8815Reb/0	involves: 129S7/SvEvBrd * C57BL/6J * FVB/N	MGI:6369716
cx4	Arid4a^tm1Alb/Arid4a^tm1Alb Arid4b^tm1Alb/Arid4b^+	involves: 129S7/SvEvBrd	MGI:3817455
cx5	Arid4b^tm1Alb/Arid4b^+ Rr70^tm1Alb/Rr70^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717489
cx6	Arid4a^tm1Alb/Arid4a^tm1Alb Arid4b^tm1Alb/Arid4b^tm1Alb	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717487
cx7	Arid4a^tm1Alb/Arid4a^tm1Alb Arid4b^tm1Alb/Arid4b^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3717488

Genotype
MGI:3717485

hm1

• Allelic Composition: Arid4b^tm1Alb/Arid4b^tm1Alb
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

mortality/aging

embryonic lethality, complete penetrance ( J:113402 )

• few embryos are recovered at E3.5 and none at E7.5

Genotype
MGI:3717486

ht2

• Allelic Composition: Arid4b^tm1Alb/Arid4b⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

genetic imprinting ( J:113402 )

• DNA methylation is normal

Genotype
MGI:6369716

cn3

• Allelic Composition: Arid4b^tm1Alb/Arid4b^tm1.1Mywu; Tg(Amh-cre)8815Reb/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB/N

reproductive system

abnormal spermatogonia morphology ( J:233398 )

♂ • only a few spermatogonia are detected in seminiferous tubules at P10

decreased male germ cell number ( J:233398 )

♂ • immunofluorescence analysis revealed a significantly reduced number of TRA98+ germ cells at P10, with only few seminiferous tubules containing germ cells by P20

♂ • no germ cells are produced in tubules that contain immature (AMH+) Sertoli cells at P20

♂ • however, population of germ cells is normal at E15.5

abnormal seminiferous tubule morphology ( J:233398 )

♂ • fewer germ cells are found in seminiferous tubules relative to controls at P10 and P20

♂ • sloughing of cells into the lumen of the tubules is clearly detected at P20

♂ • at P20, immature (AMH+) Sertoli cells are still present in many tubules, unlike in control testes; no germ cells are produced in such tubules, resulting in the formation of Sertoli cell-only tubules

♂ • at P42, some tubules are completely devoid of germ cells and contain only Sertoli cells at the basal membrane

abnormal seminiferous tubule epithelium morphology ( J:233398 )

♂ • only a thin layer of seminiferous tubule epithelium is observed at P10, unlike in control testes where thickness of the germinal epithelium is increased

dilated seminiferous tubule ( J:233398 )

♂ • large increase in seminiferous tubular diameter and widened central lumen at P30 and P42

seminiferous tubule degeneration ( J:233398 )

♂ • many seminiferous tubules undergo severe vacuolar degeneration at P42

abnormal Sertoli cell development ( J:233398 )

♂ • Sertoli cell maturation is delayed, as indicated by persistent expression of AMH (an immature Sertoli cell marker) at P10, P20, P30, and P42, despite decreases in intensity

♂ • at P20, germ cells are produced only in seminiferous tubules that do not express AMH, suggesting that immature Sertoli cells are unable to support developing germ cells even at puberty

small testis ( J:233398 )

♂ • significantly reduced testis size at 6 weeks of age

♂ • normal testis size at P2.5 with significant decrease in testis size from P10 onward

decreased testis weight ( J:233398 )

♂ • at 6 weeks of age, testis weight is reduced to ~25% of control values

abnormal testis physiology ( J:233398 )

♂ • down-regulation of androgen receptor (AR) responsive genes Rhox5 and Cldn3 in testes at P42

♂ • however, despite delayed maturation of Sertoli cells, AR expression in Sertoli cells is normal at P10, P20, and P30

increased testis apoptosis ( J:233398 )

♂ • significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays

♂ • strikingly, ~60% seminiferous tubules are TUNEL+ at P10

♂ • although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30

abnormal spermatogenesis ( J:233398 )

♂ • males exhibit delayed onset of spermatogenesis as well as impaired spermatogenic progression

azoospermia ( J:233398 )

♂ • absence of mature spermatozoa in the epididymal lumen at P42

abnormal spermatid morphology ( J:233398 )

♂ • no round spermatids are present in seminiferous tubules at P20, unlike in control testes

♂ • only round spermatids, but no elongating spermatids, are present in tubules at P30, unlike in control testes

♂ • no elongating spermatids are present in tubules at P42, unlike in control testes

♂ • only few round spermatids are present in the epididymal lumen at P42

arrest of spermatogenesis ( J:233398 )

♂ • spermatogenic arrest at the round spermatid stage

small epididymis ( J:233398 )

♂ • significantly reduced epididymis size at 6 weeks of age

decreased epididymis weight ( J:233398 )

♂ • at 6 weeks of age, epididymis weight is reduced to ~65% of control values

male infertility ( J:233398 )

♂ • males are completely infertile

homeostasis/metabolism

increased circulating follicle stimulating hormone level ( J:233398 )

♂ • males show significantly increased serum FSH levels at 2 months of age

♂ • however, serum testosterone levels are normal

increased circulating luteinizing hormone level ( J:233398 )

♂ • males show significantly increased serum LH levels at 2 months of age

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:233398 )

♂ • fewer germ cells are found in seminiferous tubules relative to controls at P10 and P20

♂ • sloughing of cells into the lumen of the tubules is clearly detected at P20

♂ • at P20, immature (AMH+) Sertoli cells are still present in many tubules, unlike in control testes; no germ cells are produced in such tubules, resulting in the formation of Sertoli cell-only tubules

♂ • at P42, some tubules are completely devoid of germ cells and contain only Sertoli cells at the basal membrane

abnormal seminiferous tubule epithelium morphology ( J:233398 )

♂ • only a thin layer of seminiferous tubule epithelium is observed at P10, unlike in control testes where thickness of the germinal epithelium is increased

dilated seminiferous tubule ( J:233398 )

♂ • large increase in seminiferous tubular diameter and widened central lumen at P30 and P42

seminiferous tubule degeneration ( J:233398 )

♂ • many seminiferous tubules undergo severe vacuolar degeneration at P42

abnormal Sertoli cell development ( J:233398 )

♂ • Sertoli cell maturation is delayed, as indicated by persistent expression of AMH (an immature Sertoli cell marker) at P10, P20, P30, and P42, despite decreases in intensity

♂ • at P20, germ cells are produced only in seminiferous tubules that do not express AMH, suggesting that immature Sertoli cells are unable to support developing germ cells even at puberty

small testis ( J:233398 )

♂ • significantly reduced testis size at 6 weeks of age

♂ • normal testis size at P2.5 with significant decrease in testis size from P10 onward

decreased testis weight ( J:233398 )

♂ • at 6 weeks of age, testis weight is reduced to ~25% of control values

abnormal testis physiology ( J:233398 )

♂ • down-regulation of androgen receptor (AR) responsive genes Rhox5 and Cldn3 in testes at P42

♂ • however, despite delayed maturation of Sertoli cells, AR expression in Sertoli cells is normal at P10, P20, and P30

increased testis apoptosis ( J:233398 )

♂ • significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays

♂ • strikingly, ~60% seminiferous tubules are TUNEL+ at P10

♂ • although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30

cellular

abnormal spermatid morphology ( J:233398 )

♂ • no round spermatids are present in seminiferous tubules at P20, unlike in control testes

♂ • only round spermatids, but no elongating spermatids, are present in tubules at P30, unlike in control testes

♂ • no elongating spermatids are present in tubules at P42, unlike in control testes

♂ • only few round spermatids are present in the epididymal lumen at P42

abnormal spermatogonia morphology ( J:233398 )

♂ • only a few spermatogonia are detected in seminiferous tubules at P10

decreased male germ cell number ( J:233398 )

♂ • immunofluorescence analysis revealed a significantly reduced number of TRA98+ germ cells at P10, with only few seminiferous tubules containing germ cells by P20

♂ • no germ cells are produced in tubules that contain immature (AMH+) Sertoli cells at P20

♂ • however, population of germ cells is normal at E15.5

azoospermia ( J:233398 )

♂ • absence of mature spermatozoa in the epididymal lumen at P42

increased testis apoptosis ( J:233398 )

♂ • significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays

♂ • strikingly, ~60% seminiferous tubules are TUNEL+ at P10

♂ • although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30

Genotype
MGI:3817455

cx4

• Allelic Composition: Arid4a^tm1Alb/Arid4a^tm1Alb; Arid4b^tm1Alb/Arid4b⁺
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

premature death ( J:141004 )

• mice exhibit increased mortality at 7 months of age

postnatal lethality ( J:141004 )

• 25% of mice die before 1 month

hematopoietic system

enlarged spleen ( J:141004 )

• in mice with acute myeloid leukemia (AML)

abnormal definitive hematopoiesis ( J:141004 )

abnormal common myeloid progenitor cell morphology ( J:141004 )

• increased in the spleen and bone marrow

abnormal leukopoiesis ( J:141004 )

• mice that exhibit acute myeloid leukemia also present with bone marrow containing a mixture of immature and dysplastic white blood cell precursors with more than 20% non-lymphoid immature forms and blasts unlike in wild-type mice

extramedullary hematopoiesis ( J:141004 )

abnormal myeloblast morphology/development ( J:141004 )

• the peripheral blood of mice with acute myeloid leukemia (AML) contains more than 20% atypical cells with morphology consistent with blasts and immature myeloid precursors unlike in wild-type mice

decreased erythrocyte cell number ( J:141004 )

• the bone marrow of mice with acute myeloid leukemia (AML)

increased erythrocyte cell number ( J:141004 )

• the spleen of mice of mice with acute myeloid leukemia (AML)

thrombocytopenia ( J:141004 )

• in the peripheral blood of mice with acute myeloid leukemia (AML)

decreased lymphocyte cell number ( J:141004 )

• in the peripheral blood of mice with acute myeloid leukemia (AML)

decreased B cell number ( J:141004 )

• the bone marrow and spleens of mice with acute myeloid leukemia (AML)

decreased T cell number ( J:141004 )

• the spleen of mice with acute myeloid leukemia (AML)

increased leukocyte cell number ( J:141004 )

• the bone marrow spleens of mice with acute myeloid leukemia (AML)

increased neutrophil cell number ( J:141004 )

• in mice with acute myeloid leukemia (AML)

increased T cell number ( J:141004 )

• the bone marrow of mice with acute myeloid leukemia (AML)

increased monocyte cell number ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit monocytosis

increased hematopoietic stem cell number ( J:141004 )

• hematopoietic stem cell populations are expanded in the bone marrow and spleen compared to in wild-type mice and Arid4a^tm1Alb homozygotes

hemophagocytosis ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit hemophagocytosis

neoplasm

increased leukemia incidence ( J:141004 )

• 83% of mice develop acute myeloid leukemia between 7 and 15 months of age

increased sarcoma incidence ( J:141004 )

• mice with acute myeloid leukemia (AML) also develop myeloid sarcomas in spleens and livers

liver/biliary system

enlarged liver ( J:141004 )

• in mice with acute myeloid leukemia (AML)

skeleton

abnormal bone marrow morphology ( J:141004 )

• mice that exhibit acute myeloid leukemia (AML) also present with bone marrow containing a mixture of immature and dysplastic white blood cell precursors with more than 20% non-lymphoid immature forms and blasts unlike in wild-type mice

• the bone marrow of mice with AML increase in granulocytes, monocytes, T lymphoid cells, and erythroid cells and a decrease in B lymphoid cells compared to in wild-type mice

• hematopoietic stem cell populations are expanded in the bone marrow compared to in wild-type mice and Arid4a^tm1Alb homozygotes

respiratory system

abnormal lung vasculature morphology ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit nucleated elements in lung blood vessels indicative of leukemic involvement

cardiovascular system

abnormal blood vessel morphology ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit nucleated elements in lung, kidney and lymph node blood vessels indicative of leukemic involvement

abnormal kidney vasculature morphology ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit nucleated elements in kidney blood vessels indicative of leukemic involvement

abnormal lung vasculature morphology ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit nucleated elements in lung blood vessels indicative of leukemic involvement

renal/urinary system

abnormal kidney vasculature morphology ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit nucleated elements in kidney blood vessels indicative of leukemic involvement

growth/size/body

decreased body weight ( J:141004 )

• at 7 weeks of age, mice weigh 30% less than wild-type mice

enlarged liver ( J:141004 )

• in mice with acute myeloid leukemia (AML)

enlarged spleen ( J:141004 )

• in mice with acute myeloid leukemia (AML)

immune system

enlarged spleen ( J:141004 )

• in mice with acute myeloid leukemia (AML)

abnormal leukopoiesis ( J:141004 )

• mice that exhibit acute myeloid leukemia also present with bone marrow containing a mixture of immature and dysplastic white blood cell precursors with more than 20% non-lymphoid immature forms and blasts unlike in wild-type mice

decreased lymphocyte cell number ( J:141004 )

• in the peripheral blood of mice with acute myeloid leukemia (AML)

decreased B cell number ( J:141004 )

• the bone marrow and spleens of mice with acute myeloid leukemia (AML)

decreased T cell number ( J:141004 )

• the spleen of mice with acute myeloid leukemia (AML)

increased leukocyte cell number ( J:141004 )

• the bone marrow spleens of mice with acute myeloid leukemia (AML)

increased neutrophil cell number ( J:141004 )

• in mice with acute myeloid leukemia (AML)

increased T cell number ( J:141004 )

• the bone marrow of mice with acute myeloid leukemia (AML)

increased monocyte cell number ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit monocytosis

hemophagocytosis ( J:141004 )

• mice with acute myeloid leukemia (AML) exhibit hemophagocytosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acute myeloid leukemia		DOID:9119	OMIM:601626	J:141004

Genotype
MGI:3717489

cx5

• Allelic Composition: Arid4b^tm1Alb/Arid4b⁺; Rr70^tm1Alb/Rr70⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

abnormal DNA methylation ( J:113402 )

abnormal imprinting ( J:113402 )

• 14 of 18 mice lack correct DNA methylation patterns

Genotype
MGI:3717487

cx6

• Allelic Composition: Arid4a^tm1Alb/Arid4a^tm1Alb; Arid4b^tm1Alb/Arid4b^tm1Alb
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

mortality/aging

perinatal lethality, complete penetrance ( J:113402 )

• mice are not viable

Genotype
MGI:3717488

cx7

• Allelic Composition: Arid4a^tm1Alb/Arid4a^tm1Alb; Arid4b^tm1Alb/Arid4b⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

abnormal DNA methylation during gametogenesis ( J:113402 )

abnormal imprinting ( J:113402 )

• 1 of 7 mice lacks correct DNA methylation patterns

• trimethylation at H4K20 is lost in all mice

maternal imprinting ( J:113402 )

• maternal imprinting is defective

reproductive system

abnormal DNA methylation during gametogenesis ( J:113402 )