Phenotypes associated with this allele

• Allele Symbol: Rhbdf2^tm1Mak
• Allele Name: targeted mutation 1, Tak Mak
• Allele ID: MGI:5309136
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rhbdf2^tm1Mak/Rhbdf2^tm1Mak	B6.129P2-Rhbdf2^tm1Mak	MGI:5309137
hm2	Rhbdf2^tm1Mak/Rhbdf2^tm1Mak	involves: 129P2/OlaHsd * C57BL/6	MGI:5803829
cx3	Rhbdf1^tm1b(EUCOMM)Wtsi/Rhbdf1^tm1b(EUCOMM)Wtsi Rhbdf2^tm1Mak/Rhbdf2^tm1Mak	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * FVB/N	MGI:5803831

Genotype
MGI:5309137

hm1

• Allelic Composition: Rhbdf2^tm1Mak/Rhbdf2^tm1Mak
• Genetic Background: B6.129P2-Rhbdf2^tm1Mak

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

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:179653 )

• succumb more rapidly following infection with Listeria monocytogenes compared to wild-type controls

• die following infection with Listeria monocytogenes doses that are non-lethal in wild-type controls

decreased susceptibility to infection induced morbidity/mortality ( J:179653 )

• prolonged survival following LPS and D-galactosamine treatment

immune system

abnormal B cell physiology ( J:179653 )

• B cells stimulated with the nucleotide analog 2' (3')-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP) show inhibited CD62L shedding

abnormal immune serum protein physiology ( J:179653 )

decreased circulating tumor necrosis factor level ( J:179653 )

• following stimulation with LPS or LPS and D-galactosamine

decreased tumor necrosis factor secretion ( J:179653 )

• in culture LPS stimulated thioglycollate-elicited peritoneal macrophages shed less TNF into the media despite showing similar levels of mRNA upregulation and have increased levels of membrane bound protein

increased susceptibility to bacterial infection ( J:179653 )

• higher bacterial loads in the spleen, liver, kidney, and brain following infection with Listeria monocytogenes compared to wild-type controls

increased susceptibility to bacterial infection induced morbidity/mortality ( J:179653 )

• succumb more rapidly following infection with Listeria monocytogenes compared to wild-type controls

• die following infection with Listeria monocytogenes doses that are non-lethal in wild-type controls

decreased susceptibility to infection induced morbidity/mortality ( J:179653 )

• prolonged survival following LPS and D-galactosamine treatment

liver/biliary system

abnormal liver physiology ( J:179653 )

• decrease in amount of liver damage induced by LPS and D-galactosamine treatment

homeostasis/metabolism

decreased circulating tumor necrosis factor level ( J:179653 )

• following stimulation with LPS or LPS and D-galactosamine

hematopoietic system

abnormal B cell physiology ( J:179653 )

• B cells stimulated with the nucleotide analog 2' (3')-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP) show inhibited CD62L shedding

Genotype
MGI:5803829

hm2

• Allelic Composition: Rhbdf2^tm1Mak/Rhbdf2^tm1Mak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

abnormal leukocyte physiology ( J:221411 )

• phorbol ester (PMA)-stimulated shedding of CD62L (L-selectin) is almost completely abolished in circulating CD45^high leukocytes isolated from mutant brain, unlike in wild-type brain leukocytes

abnormal microglial cell physiology ( J:221411 )

• LPS-stimulated release of the ADAM17 substrate TNF is almost undetectable in mutant resident microglia (CD45^lowCD11b^highF4/80⁺Ly6C^low cells), unlike in wild-type microglia

decreased tumor necrosis factor secretion ( J:221411 )

• LPS-stimulated release of the ADAM17 substrate TNF is almost undetectable in mutant resident microglia, unlike in wild-type microglia

hematopoietic system

abnormal leukocyte physiology ( J:221411 )

• phorbol ester (PMA)-stimulated shedding of CD62L (L-selectin) is almost completely abolished in circulating CD45^high leukocytes isolated from mutant brain, unlike in wild-type brain leukocytes

abnormal microglial cell physiology ( J:221411 )

• LPS-stimulated release of the ADAM17 substrate TNF is almost undetectable in mutant resident microglia (CD45^lowCD11b^highF4/80⁺Ly6C^low cells), unlike in wild-type microglia

nervous system

abnormal microglial cell physiology ( J:221411 )

• LPS-stimulated release of the ADAM17 substrate TNF is almost undetectable in mutant resident microglia (CD45^lowCD11b^highF4/80⁺Ly6C^low cells), unlike in wild-type microglia

vision/eye

vision/eye phenotype ( J:221411 )

N • mice do not exhibit open eyes at birth

cardiovascular system

cardiovascular system phenotype ( J:221411 )

N • newborn mice display normal aortic, pulmonic, and tricuspid heart valves

skeleton

skeleton phenotype ( J:221411 )

N • newborn mice display normal femoral and humeral growth plates

Genotype
MGI:5803831

cx3

• Allelic Composition: Rhbdf1^{tm1b(EUCOMM)Wtsi}/Rhbdf1^{tm1b(EUCOMM)Wtsi}; Rhbdf2^tm1Mak/Rhbdf2^tm1Mak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6N * FVB/N
• Cell Lines: EPD0577_2_H04

Failure of eyelid closure, enlarged aortic, pulmonic, and tricuspid heart valves, and enlarged zone of hypertrophic chondrocytes in growth plates of Rhbdf1^{tm1b(EUCOMM)Wtsi}/Rhbdf1^{tm1b(EUCOMM)Wtsi} Rhbdf2^tm1Mak/Rhbdf2^tm1Mak (iR1/2-/-) and Adam17^tm1.1Bbl/Adam17^tm1.1Bbl mice.

mortality/aging

perinatal lethality ( J:221411 )

• mice are born at the expected Mendelian ratio but show perinatal lethality

vision/eye

failure of eyelid fusion ( J:221411 )

• mice exhibit failure of eyelid closure

eyelids open at birth ( J:221411 )

• mice are born with open eyes

cardiovascular system

thick tricuspid valve cusps ( J:221411 )

• at P1, tricuspid valve leaflets are thickened in relationship to their length

enlarged tricuspid valve ( J:221411 )

• newborn (P1) mice display enlarged tricuspid heart valves

• however, mitral valves are normal

thick aortic valve cusps ( J:221411 )

• newborn (P1) mice show a significant increase in the average width relative to the length of individual aortic valve leaflets

enlarged aortic valve ( J:221411 )

• newborn (P1) mice display enlarged aortic heart valves

thick pulmonary valve cusps ( J:221411 )

• at P1, pulmonic valve leaflets are thickened in relationship to their length

enlarged pulmonary valve ( J:221411 )

• newborn (P1) mice display enlarged pulmonic heart valves

skeleton

increased width of hypertrophic chondrocyte zone ( J:221411 )

• newborn (P1) mice display an enlarged zone of hypertrophic chondrocytes in the femoral and humoral growth plates