Phenotypes associated with this allele

• Allele Symbol: Hip1^{tm5.1(HIP1)Tsr}
• Allele Name: targeted mutation 5.1, Theodora S Ross
• Allele ID: MGI:6280488
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hip1^tm5.1(HIP1)Tsr/Hip1^tm5.1(HIP1)Tsr	involves: C57BL/6	MGI:6719554
cn2	Hip1^tm5.1(HIP1)Tsr/Hip1^tm5.1(HIP1)Tsr Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * C57BL/6J * CBA/J	MGI:6719558
cn3	Hip1^tm5.1(HIP1)Tsr/Hip1^tm5.1(HIP1)Tsr Tg(GFAP-cre)25Mes/0	involves: C57BL/6 * FVB/N	MGI:6719557
cx4	Gdpd3^em1Tsr/Gdpd3^em1Tsr Hip1^tm5.1(HIP1)Tsr/Hip1^tm5.1(HIP1)Tsr	involves: C57BL/6 * C57BL/6J	MGI:6719561

Genotype
MGI:6719554

hm1

• Allelic Composition: Hip1^{tm5.1(HIP1)Tsr}/Hip1^{tm5.1(HIP1)Tsr}
• Genetic Background: involves: C57BL/6

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

growth/size/body

decreased body weight ( J:267987 )

• although overtly normal at birth, all mice exhibit decreased body weight by 6 months of age

weight loss ( J:267987 )

skeleton

abnormal vertebral column morphology ( J:267987 )

• all mice develop severe spinal defects

lordokyphosis ( J:267987 )

• all mice exhibit severe kypholordosis by 6 months of age

• transplantation of wild-type bone marrow into irradiated knockout mice does not prevent development of kypholordosis

homeostasis/metabolism

abnormal amino acid level ( J:267987 )

• homocysteine level is significantly increased in the brain, liver, kidney and spleen, with the largest increase observed in liver (13.41-fold)

decreased cystathionine level ( J:267987 )

• cystathionine level is significantly reduced in the brain, liver and kidney

abnormal enzyme/coenzyme level ( J:267987 )

• mRNA expression of Gdpd3 (glycerophosphodiester phosphodiesterase domain containing 3) is significantly reduced in all tissues tested (brain, liver, kidney, lung and spleen), with a similar reduction seen in both young and old (kypholordotic) mice

decreased acetylcholine level ( J:267987 )

• acetylcholine level is significantly decreased in the liver and kidney, with the largest reduction observed in liver (0.55-fold)

decreased phosphocholine level ( J:267987 )

• phosphocholine level is significantly reduced in the kidney, lung, liver and spleen, but not in brain

• largest reduction of phosphocholine level is observed in liver (0.41-fold)

• however, total choline levels are normal in all tissues tested and no changes are noted in lysophosphatidylcholine or glycerophosphocholine (GPC)

abnormal vitamin homeostasis ( J:267987 )

• pyridoxamine (a vitamer of vitamin B6) is significantly reduced in all tissues tested (brain, liver, kidney, lung and spleen)

• however, serum vitamin B6 levels are normal

abnormal metabolism ( J:267987 )

• mice exhibit altered levels of choline-related metabolites, including a striking reduction in phosphocholine levels and elevated homocysteine levels

• additional alterations are observed in acetylcholine, betaine aldehyde, trimethylglycine/betaine, and dimethylglycine levels

• S-adenosylhomocysteine (SAH) levels are increased and S-adenosylmethionine (SAM) levels are decreased in several tissues

• however, histone methylation is normal

Genotype
MGI:6719558

cn2

• Allelic Composition: Hip1^{tm5.1(HIP1)Tsr}/Hip1^{tm5.1(HIP1)Tsr}; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA/J

growth/size/body

growth/size/body region phenotype ( J:267987 )

N • mice treated with pIpC at 6 weeks of age (to induce human HIP1 expression in the adult hematopoietic system, liver, and kidney) exhibit normal weight at 5.5-6 months of age, indicating rescue of the weight loss observed in Hip1^{tm5.1(HIP1)Tsr} homozygotes

skeleton

skeleton phenotype ( J:267987 )

N • mice treated with pIpC at 6 weeks of age exhibit no spinal defects at 4 months of age, indicating rescue of the kypholordotic phenotype observed in Hip1^{tm5.1(HIP1)Tsr} homozygotes

Genotype
MGI:6719557

cn3

• Allelic Composition: Hip1^{tm5.1(HIP1)Tsr}/Hip1^{tm5.1(HIP1)Tsr}; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: C57BL/6 * FVB/N

skeleton

lordokyphosis ( J:267987 )

• unexpectedly, mice exhibit severe kypholordosis at 6 months of age, indicating that brain-specific expression of human HIP1 does not rescue the spinal phenotype

Genotype
MGI:6719561

cx4

• Allelic Composition: Gdpd3^em1Tsr/Gdpd3^em1Tsr; Hip1^{tm5.1(HIP1)Tsr}/Hip1^{tm5.1(HIP1)Tsr}
• Genetic Background: involves: C57BL/6 * C57BL/6J

skeleton

lordokyphosis ( J:267987 )

• mice exhibit a significantly earlier onset of kypholordosis with a smaller angle of the thoracic curvature noted at 10 months of age, indicating an accelerated and more severe kypholordotic phenotype relative to single Hip1^{tm5.1(HIP1)Tsr} homozygotes