Phenotypes associated with this allele

• Allele Symbol: Bcr^tm1Hkp
• Allele Name: targeted mutation 1, Nora Heisterkamp
• Allele ID: MGI:2154396
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bcr^tm1Hkp/Bcr^tm1Hkp	involves: 129S2/SvPas	MGI:3839985
cx2	Abr^tm1Jhg/Abr^tm1Jhg Bcr^tm1Hkp/Bcr^tm1Hkp	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Black Swiss * C57BL/6	MGI:2653904

Genotype
MGI:3839985

hm1

• Allelic Composition: Bcr^tm1Hkp/Bcr^tm1Hkp
• Genetic Background: involves: 129S2/SvPas

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

immune system

increased leukocyte cell number ( J:23804 )

• in the kidney and liver 6 hours after LPS-exposure unlike similarly treated wild-type mice

increased neutrophil cell number ( J:23804 )

• 6 hours after LPS-exposure, mice exhibit a 2- to 3- fold increase in circulating neutrophils that is sustained and more pronounced than in similarly treated wild-type mice

abnormal neutrophil physiology ( J:23804 )

• following activation with phorbol myristate acetate (PMA) or PMA and N-formyl-Met-Leu-Phe, neutrophils exhibit a 100% increase in respiratory burst compared to similarly treated wild-type mice

• neutrophils are more easily primed and activated compared to wild-type cells

• neutrophils exhibit spontaneous activation unlike wild-type cells

increased susceptibility to endotoxin shock ( J:23804 )

• mice exposed to LPS develop septic shock lasting at least 4 days accompanied by weight loss and intestinal edema before onset of recovery unlike similarly treated wild-type mice that recover within 24 hours of exposure

• unlike in wild-type mice, LPS exposure leads to extensive damage in multiple organs including the ileum, kidney, and liver

• however, removal of neutrophils using cyclophosphamide treatment restores normal response to LPS

• LPS-exposed mice exhibit increased plasma lactate dehydrogenase, aspartate and alanine aminotransferase, and blood nitrogen urea compared to similarly treated wild-type mice

sepsis ( J:23804 )

• mice exposed to LPS develop septic shock lasting at least 4 days before recovery unlike similarly treated wild-type mice

homeostasis/metabolism

intestinal edema ( J:23804 )

• following LPS exposure

increased blood urea nitrogen level ( J:23804 )

• following LPS exposure

increased circulating alanine transaminase level ( J:23804 )

• following LPS exposure

increased circulating aspartate transaminase level ( J:23804 )

• following LPS exposure

increased circulating lactate dehydrogenase level ( J:23804 )

• higher plasma LDH levels following LPS exposure

renal/urinary system

abnormal renal glomerulus morphology ( J:23804 )

• LPS-treated mice exhibit glomerular collapse as early as 6 hours post-exposure unlike similarly treated wild-type mice

abnormal proximal convoluted tubule morphology ( J:23804 )

• LPS-treated mice exhibit extensive vacuolization of proximal convoluted tubules unlike similarly treated wild-type mice

renal necrosis ( J:23804 )

• LPS-treated mice exhibit cortical necrosis unlike similarly treated wild-type mice

liver/biliary system

abnormal liver parenchyma morphology ( J:23804 )

• 72 hours after LPS-exposure, mice exhibit fatty vacuolization in the liver parenchyma unlike similarly treated wild-type mice

digestive/alimentary system

abnormal ileum morphology ( J:23804 )

• unlike in wild-type mice, LPS-treated mice exhibit the presence of debris and mucus plugs in the intestinal lumen and in between microvilli indicating necrosis of mucosal epithelial cells at 24 hours post-exposure

intestinal edema ( J:23804 )

• following LPS exposure

growth/size/body

weight loss ( J:23804 )

• following LPS exposure

hematopoietic system

abnormal definitive hematopoiesis ( J:23804 )

• 72 hours after LPS-exposure, hematopoiesis shifts to granulopoiesis unlike in similarly treated wild-type mice

increased leukocyte cell number ( J:23804 )

• in the kidney and liver 6 hours after LPS-exposure unlike similarly treated wild-type mice

increased neutrophil cell number ( J:23804 )

• 6 hours after LPS-exposure, mice exhibit a 2- to 3- fold increase in circulating neutrophils that is sustained and more pronounced than in similarly treated wild-type mice

abnormal neutrophil physiology ( J:23804 )

• following activation with phorbol myristate acetate (PMA) or PMA and N-formyl-Met-Leu-Phe, neutrophils exhibit a 100% increase in respiratory burst compared to similarly treated wild-type mice

• neutrophils are more easily primed and activated compared to wild-type cells

• neutrophils exhibit spontaneous activation unlike wild-type cells

Genotype
MGI:2653904

cx2

• Allelic Composition: Abr^tm1Jhg/Abr^tm1Jhg; Bcr^tm1Hkp/Bcr^tm1Hkp
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * Black Swiss * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:72425 )

• the expected numbers of mutants are seen immediately after birth, however a reduced frequency is seen one day after birth

behavior/neurological

impaired balance ( J:108010 )

• mutants frequently lose their balance

impaired coordination ( J:72425 , J:108010 )

• clumsy movement, stumbling (J:72425)

• poor motor coordination (J:108010)

impaired swimming ( J:108010 )

• unable to swim

hyperactivity ( J:72425 , J:108010 )

circling ( J:72425 , J:108010 )

nervous system

abnormal cerebellum morphology ( J:72425 )

abnormal cerebellar foliation ( J:72425 )

• defective foliation is seen as early as P11, with abnormal anterior foliation pattern including partial fusion

ectopic cerebellar granule cells ( J:72425 )

• large numbers of granule neurons are found in an abnormal location on the surface of the molecular layer of the cerebellum

• ectopic granule cells are found in all folia, but numbers are especially high in the anterior folia of the cerebellar vermis and anterior medullary velum

abnormal CNS glial cell morphology ( J:72425 )

• spontaneous glial hypertrophy

• premature termination and disorganization of the end-feet of the Bergmann fibers

abnormal radial glial cell morphology ( J:72425 )

• disorganization of radial glia on the cerebellar cortex at P5

abnormal astrocyte morphology ( J:72425 )

• mutants display aberrant Gfap-positive astroglia on the surface of the cerebellar external granule layer at P5; glial processes often lose their radial orientation when they approach the pial surface and display abnormal end-feet, that fail to form a well-defined glial boundary

• serum starved astrocytes are 20% more spread than control cells and upon epidermal growth factor stimulation, mutant cells project distinct Gfap-positive protrusions not seen in controls

gliosis ( J:72425 )

• reactive gliosis in the midbrain in response to kainic acid exposure

abnormal astrocyte physiology ( J:72425 )

• astroglia are hyperresponsive to stimulation with epidermal growth factor and lipopolysaccharide

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:108010 )

N • mutants are not deaf as they respond to the Preyer reflex test at 1 year of age and exhibit normal cochlea, semicircular canals, organ of Corti, and vestibular ganglia and nerves

abnormal inner ear development ( J:108010 )

• vacuolation is seen under or within the utricular and saccular epithelium at E13.5, indicating abnormal vestibular development

abnormal inner ear vestibule morphology ( J:108010 )

• dysplasia of the vestibular compartment of the inner ear

• reduction in the sensory epithelium in both the saccule and the utricle

abnormal utricle morphology ( J:108010 )

• utricle is grossly abnormal

abnormal vestibular saccule morphology ( J:108010 )

• vacuolation is seen on both sides of the saccular epithelium at 3 weeks of age

• saccule is grossly malformed, showing detachment of the epithelial layer from the underlying connective tissue

decreased otolith number ( J:108010 )

• otoconia are either missing or reduced in number in the saccule

absent otoliths ( J:72425 , J:108010 )

• absence of vestibular otoconia (J:72425)

• total loss of otoconia in the utricle (J:108010)

• otoconia are either missiong or reduced in number in the saccule (J:108010)

enlarged otoliths ( J:108010 )

• when present in the saccule, otoconia are abnormally large

cellular

abnormal radial glial cell morphology ( J:72425 )

• disorganization of radial glia on the cerebellar cortex at P5