Phenotypes associated with this allele

• Allele Symbol: Hip1^tm3Tsr
• Allele Name: targeted mutation 3, Theodora S Ross
• Allele ID: MGI:3044458
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hip1^tm3Tsr/Hip1^tm3Tsr	involves: 129X1/SvJ * C57BL/6	MGI:3044673
cx2	Hip1^tm3Tsr/Hip1^tm3Tsr Hip1r^tm1Tsr/Hip1r^tm1Tsr	involves: 129X1/SvJ	MGI:6719555
cx3	Hip1^tm3Tsr/Hip1^tm3Tsr Hip1r^tm1Tsr/Hip1r^tm1Tsr	involves: 129X1/SvJ * C57BL/6	MGI:3045699
cx4	Hip1^tm3Tsr/Hip1^tm5.2(HIP1)Tsr Hip1r^tm1Tsr/Hip1r^tm1Tsr	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:6719556

Genotype
MGI:3044673

hm1

• Allelic Composition: Hip1^tm3Tsr/Hip1^tm3Tsr
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

cellular

abnormal spermatid morphology ( J:90400 )

♂ • apoptosis of postmeiotic spermatids

mortality/aging

perinatal lethality, incomplete penetrance ( J:90400 )

• incomplete penetrance

• though mice were present in Mendelian ratios between E11 and E18.5, homozygotes were underrepresented after E18.5

growth/size/body

weight loss ( J:90400 )

• associated with kypholordosis

hematopoietic system

hematopoietic system phenotype ( J:90400 )

N • normal peripheral blood count

N • normal frequency of lymphoid progenitors

N • increased resistance to 5-fluorouracil (5-FU) induced myeloablation relative to wild-type

absent common myeloid progenitor cells ( J:90400 )

• reduced frequency of early progenitor (CFU-GEMM) colonies in 85% of mice

• CFU-GEMM colony sizes were normal

• normal frequency of clonogenic hematopoietic progenitors, BFU-E, and CFU-GM

reproductive system

abnormal spermatid morphology ( J:90400 )

♂ • apoptosis of postmeiotic spermatids

testis degeneration ( J:90400 )

♂ • testicular degeneration; more severe than in Hip1^{tm1Tsr/tm1Tsr} mice

reduced male fertility ( J:90400 )

♂ • while most males showed profoundly reduced fertility, some were fertile

skeleton

skeleton phenotype ( J:90400 )

N • neither osteoporosis or osteoarthritis was observed in mice exhibiting kypholordosis

N • no developmental, degenerative skeletal, or cartilage defects

lordokyphosis ( J:90400 )

• kypholordosis was observed as early as 4 months of age and was initially more penetrant in females (particularly pregnant ones), however by 1 year of age 100% exhibited the abnormality

• associated with severe weight loss as it progressed

vision/eye

nuclear cataract ( J:90400 )

• nuclear cataracts associated with cortical abnormalities

small lens ( J:90400 )

• apoptotic cells were observed in the lens

microphthalmia ( J:90400 )

• observed macroscopically in 71% of mice, but closer examination revealed that 100% of the mice had small eyes

• evident at 3 weeks of age, suggesting that the abnormality is due to impaired development rather than degeneration

nervous system

nervous system phenotype ( J:90400 )

N • though CNS defects were suspected to be the cause of the observed kypholordosis, no defects were observed

endocrine/exocrine glands

testis degeneration ( J:90400 )

♂ • testicular degeneration; more severe than in Hip1^{tm1Tsr/tm1Tsr} mice

Genotype
MGI:6719555

cx2

• Allelic Composition: Hip1^tm3Tsr/Hip1^tm3Tsr; Hip1r^tm1Tsr/Hip1r^tm1Tsr
• Genetic Background: involves: 129X1/SvJ

skeleton

lordokyphosis ( J:267987 )

• mice exhibit more severe kypholordosis than age-matched than Hip1^{tm5.1(HIP1)Tsr} homozygotes

Genotype
MGI:3045699

cx3

• Allelic Composition: Hip1^tm3Tsr/Hip1^tm3Tsr; Hip1r^tm1Tsr/Hip1r^tm1Tsr
• Genetic Background: involves: 129X1/SvJ * C57BL/6

growth/size/body

decreased body size ( J:89961 )

• although not apparent at birth, dwarfism is noticeable by early adulthood

decreased body weight ( J:89961 )

• reduced body mass

mortality/aging

premature death ( J:89961 )

• spontaneous death in two mice at 3 months of age

skeleton

abnormal vertebral column morphology ( J:89961 )

• skeletal disorganization in both thoracic and lumbar spinal regions at 13 weeks of age

abnormal spine curvature ( J:89961 )

• abnormalities in spinal curvature noticeable as early as 2 weeks of age

• all mice exhibit the deformity by weaning

lordokyphosis ( J:89961 )

• dramatically accelerated kypholordosis relative to Hip1^tm3Tsr homozygotes

abnormal vertebral body morphology ( J:89961 )

• vertebral bodies show asymmetry with encroachment of cartilage into areas normally occupied by bone marrow

behavior/neurological

hunched posture ( J:89961 )

Genotype
MGI:6719556

cx4

• Allelic Composition: Hip1^tm3Tsr/Hip1^{tm5.2(HIP1)Tsr}; Hip1r^tm1Tsr/Hip1r^tm1Tsr
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

skeleton

skeleton phenotype ( J:267987 )

N • mice exhibit no kypholordotic spine, indicating rescue of the spinal phenotype by a single copy of human HIP1