Phenotypes associated with this allele

• Allele Symbol: Mapk8^tm1Rjd
• Allele Name: targeted mutation 1, Roger J Davis
• Allele ID: MGI:3775057
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Mapk8^tm1Rjd/Mapk8^tm1Rjd Mapk9^tm2.1Rjd/Mapk9^tm2.1Rjd Lyz2^tm1(cre)Ifo/Lyz2^+	B6J.Cg-Lyz2^tm1(cre)Ifo Mapk9^tm2.1Rjd Mapk8^tm1Rjd	MGI:5882343
cn2	Mapk8^tm1Rjd/Mapk8^tm1Rjd Mapk9^tm1Flv/Mapk9^tm1Flv Tg(Col2a1-cre)1Bhr/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL	MGI:7279112
cn3	Mapk8^tm1Rjd/Mapk8^tm1Rjd Mapk9^tm1Flv/Mapk9^tm1Flv	involves: 129S2/SvPas * C57BL/6J	MGI:3811225

Genotype
MGI:5882343

cn1

• Allelic Composition: Mapk8^tm1Rjd/Mapk8^tm1Rjd; Mapk9^tm2.1Rjd/Mapk9^tm2.1Rjd; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: B6J.Cg-Lyz2^tm1(cre)Ifo Mapk9^tm2.1Rjd Mapk8^tm1Rjd

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

growth/size/body

decreased lean body mass ( J:192551 )

• chow-fed mice exhibit a slight but significant reduction in lean mass relative to controls

• however, mice fed a high fat diet (HFD) for 4 weeks show no differences in lean mass relative to HFD-fed controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:192551 )

N • chow-fed mice exhibit comparable insulin and glucose tolerance and blood concentrations of glucose and insulin relative to chow-fed controls

N • HFD-fed mice show comparable diet-induced obesity with no differences in blood glycerol and free fatty acids (FFA) levels relative to HFD-fed controls

abnormal circulating cytokine level ( J:192551 )

• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated cytokine levels relative to chow-fed control mice

abnormal circulating chemokine level ( J:192551 )

• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated chemokine levels relative to chow-fed control mice

abnormal glucose homeostasis ( J:192551 )

• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced steady-state glucose infusion rate, clamp hepatic glucose production, and insulin-stimulated whole-body glucose turnover relative to similarly-fed control mice

increased insulin secretion ( J:192551 )

• HFD-fed mice show a significant increase in glucose-induced insulin secretion both in vitro and in vivo relative to HFD-fed controls

decreased circulating glucose level ( J:192551 )

• mice are protected from HFD-induced hyperglycemia, unlike HFD-fed controls

decreased circulating insulin level ( J:192551 )

• mice are protected from HFD-induced hyperinsulinemia, unlike HFD-fed controls

abnormal gluconeogenesis ( J:192551 )

• HFD-fed mice show significantly reduced gluconeogenesis relative to HFD-fed controls

improved glucose tolerance ( J:192551 )

• HFD-fed mice show improved glucose tolerance relative to HFD-fed controls

abnormal glycogen homeostasis ( J:192551 )

• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced whole-body glycogen plus lipid synthesis relative to similarly-fed control mice

increased insulin sensitivity ( J:192551 )

• HFD-fed mice show improved insulin tolerance relative to HFD-fed controls

• hyperinsulinemic-euglycemic clamp studies revealed that increased whole-body insulin sensitivity is due to significant improvements in glucose infusion rates, hepatic insulin action, clamp hepatic glucose production, insulin-stimulated whole body glucose turnover, and whole-body glycogen plus lipid synthesis relative to control mice

• after overnight fasting, HFD-fed mice fail to suppress insulin-stimulated Akt activation in the liver, white adipose tissue and skeletal muscle, unlike similarly treated HFD-fed control mice

• protection of HFD-fed mice against insulin resistance is associated with reduced tissue infiltration by macrophages

abnormal lipid homeostasis ( J:192551 )

• hyperinsulinemic-euglycemic clamp studies revealed that mice fed either a regular chow or a HFD show a significantly enhanced whole-body glycogen plus lipid synthesis relative to similarly-fed control mice

abnormal chemokine level ( J:192551 )

• HFD-fed mice show significantly reduced chemokine expression relative to HFD-fed controls

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of chemokine (Ccl2 and Ccl5) genes relative to control BMDMs

endocrine/exocrine glands

decreased pancreatic beta cell proliferation ( J:192551 )

• HFD-fed mice show a significant reduction in pancreatic beta cell proliferation relative to HFD-fed controls

small pancreatic islets ( J:192551 )

• HFD-fed mice show a significant reduction in pancreatic islet area relative to HFD-fed controls

• however, chow-fed mice show no differences in islet area relative to chow-fed controls

increased insulin secretion ( J:192551 )

• HFD-fed mice show a significant increase in glucose-induced insulin secretion both in vitro and in vivo relative to HFD-fed controls

immune system

abnormal macrophage differentiation ( J:192551 )

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs

• however, M2 differentiation appears unaffected

decreased macrophage cell number ( J:192551 )

• HFD-fed mice show a significant decrease in the total number of F4/80+ adipose tissue macrophages (ATMs) and reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls

• HFD-fed mice also show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls

• HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls

• chow-fed mice show no differences in total, M1- or M2-polarized ATM number relative to chow-fed controls

abnormal macrophage physiology ( J:192551 )

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of M1 marker genes (Ccr7 and Cd11c), chemokines (Ccl2 and Ccl5), and cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs

• similar defects are detected in LPS-stimulated macrophages

impaired macrophage chemotaxis ( J:192551 )

• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls

• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls

• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls

decreased macrophage cytokine production ( J:192551 )

• upon IFN-gamma stimulation, isolated BMDMs show decreased expression of cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs

abnormal circulating cytokine level ( J:192551 )

• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated cytokine levels relative to chow-fed control mice

abnormal circulating chemokine level ( J:192551 )

• upon LPS stimulation, chow-fed mice show significantly reduced blood M1-associated chemokine levels relative to chow-fed control mice

abnormal chemokine level ( J:192551 )

• HFD-fed mice show significantly reduced chemokine expression relative to HFD-fed controls

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of chemokine (Ccl2 and Ccl5) genes relative to control BMDMs

decreased inflammatory response ( J:192551 )

• HFD-fed mice show significantly reduced hepatic inflammation relative to HFD-fed controls

hematopoietic system

abnormal macrophage differentiation ( J:192551 )

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs

• however, M2 differentiation appears unaffected

decreased macrophage cell number ( J:192551 )

• HFD-fed mice show a significant decrease in the total number of F4/80+ adipose tissue macrophages (ATMs) and reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls

• HFD-fed mice also show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls

• HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls

• chow-fed mice show no differences in total, M1- or M2-polarized ATM number relative to chow-fed controls

abnormal macrophage physiology ( J:192551 )

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show decreased expression of M1 marker genes (Ccr7 and Cd11c), chemokines (Ccl2 and Ccl5), and cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs

• similar defects are detected in LPS-stimulated macrophages

impaired macrophage chemotaxis ( J:192551 )

• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls

• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls

• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls

decreased macrophage cytokine production ( J:192551 )

• upon IFN-gamma stimulation, isolated BMDMs show decreased expression of cytokine genes (Il1beta, Il6, and Tnf) relative to control BMDMs

cellular

abnormal macrophage differentiation ( J:192551 )

• upon IFN-gamma stimulation, isolated bone marrow-derived macrophages (BMDMs) show reduced M1 differentiation and expression of the cell surface marker CD11c relative to control BMDMs

• however, M2 differentiation appears unaffected

impaired macrophage chemotaxis ( J:192551 )

• HFD-fed mice show significantly reduced accumulation of M1-polarized (F4/80+CD11c+CD206-) ATMs in adipose tissue relative to HFD-fed controls

• HFD-fed mice show decreased accumulation of M1 tissue macrophages in the liver relative to HFD-fed controls

• however, HFD-fed mice show no significant difference in the accumulation of M2-polarized ATMs (F4/80+CD11c-CD206+) relative to HFD-fed controls

decreased pancreatic beta cell proliferation ( J:192551 )

• HFD-fed mice show a significant reduction in pancreatic beta cell proliferation relative to HFD-fed controls

Genotype
MGI:7279112

cn2

• Allelic Composition: Mapk8^tm1Rjd/Mapk8^tm1Rjd; Mapk9^tm1Flv/Mapk9^tm1Flv; Tg(Col2a1-cre)1Bhr/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * SJL

mortality/aging

premature death ( J:277201 )

• need to be euthanized at approximately 10 weeks of age due to urinary retention and paraphimosis

renal/urinary system

paraphimosis ( J:277201 )

ischuria ( J:277201 )

• urinary retention

skeleton

abnormal knee joint morphology ( J:277201 )

• the articular cartilage thickness, the width of the joint at the level of the femoral condyles, and the height of the tibial plateau are decreased

abnormal sternebra morphology ( J:277201 )

• enlargement of the growth plate

sternebra fusion ( J:277201 )

• at 10 weeks of age

abnormal sternocostal joint morphology ( J:277201 )

• separation at the joints is not well defined at 10 weeks of age

abnormal intervertebral disk morphology ( J:277201 )

• ectopic ossification localized in the caudal thoracic and thoracic spine at 4 weeks of age

• the typical lamellar structure of the annulus fibrosus is completely absent at 4 weeks of age

• at 10 weeks of age in the proximal thoracic spine (approximately cranial to T9) disks are replaced by a proteoglycan-rich cartilaginous tissue that extends beyond the disk and appears to connect the distal and proximal growth plates of adjacent vertebral bodies

• at E15.5 and E17.5, the annulus fibrosus is populated by larger, chondrocyte-like cells with altered alignment of the collagen fibers in the laminae

• increased annulus fibrosus width for both dorsal and ventral regions at E17.5

abnormal nucleus pulposus morphology ( J:277201 )

• reduced in size at 4 weeks of age

calcified intervertebral disk ( J:277201 )

• seen at P11

• at 10 weeks of age most of the area of the disks is completely replaced with bone and cartilage in the lumbar and caudal thoracic spine

scoliosis ( J:277201 )

• seen at 4 weeks of age with Cobb angles ranging from 40 to 92 degrees

abnormal vertebrae morphology ( J:277201 )

• ectopic ossification in multiple structures of the vertebrae including the transverse and spinous processes

abnormal vertebral epiphyseal plate morphology ( J:277201 )

• decreased length at E17.5

vertebral fusion ( J:277201 )

• fused vertebrae with no space where the intervertebral disks should be

• fusions in the transverse and spinous processes are seen at P11 with the most advanced lesions seen in the lumbar spine

fusion of vertebral arches ( J:277201 )

• seen at E17.5 along with abnormally shaped primary ossification centers

fusion of vertebral bodies ( J:277201 )

• fusions of bodies and posterior elements are detected in the lumbar and thoracic spine

growth/size/body

decreased body size ( J:277201 )

distended abdomen ( J:277201 )

• at weaning

behavior/neurological

abnormal gait ( J:277201 )

• at weaning

limbs/digits/tail

abnormal knee joint morphology ( J:277201 )

• the articular cartilage thickness, the width of the joint at the level of the femoral condyles, and the height of the tibial plateau are decreased

abnormal tail position or orientation ( J:277201 )

• upward tail orientation

reproductive system

paraphimosis ( J:277201 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
scoliosis		DOID:0060249		J:277201

Genotype
MGI:3811225

cn3

• Allelic Composition: Mapk8^tm1Rjd/Mapk8^tm1Rjd; Mapk9^tm1Flv/Mapk9^tm1Flv
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

cellular

increased fibroblast apoptosis ( J:131766 )

• following treatment with an andenoviral cre, mouse embryonic fibroblasts exhibit reduced UV- or TNF-stimulated apoptosis compared to wild-type cells