INT122852

Context Info Confidence 0.76 First Reported 2004 Last Reported 2007 Negated 2 Speculated 0 Reported most in Body Documents 7 Total Number 18 Disease Relevance 13.51 Pain Relevance 1.64

peptidase activity (Prss1) extracellular space (Prss1)

Anatomy Link Frequency abdomen 1 acinar cells 1 Prss1 (Mus musculus) Prss1 - R122H (2)

Pain Link Frequency Relevance Heat Inflammation 97 96.72 cytokine 108 93.80 Chronic pancreatitis 78 90.40 Hyperalgesia 3 75.00 cva 12 49.56 Root ganglion neuron 1 47.76 qutenza 2 44.56 nociceptor 2 25.00 allodynia 1 25.00 Thermal hyperalgesia 1 25.00

Disease Link Frequency Relevance Heat Targeted Disruption 492 99.98 Apoptosis 116 99.86 Pancreatitis 561 98.84 Disease 81 98.60 Death 24 97.96 INFLAMMATION 96 96.72 Pancreatic Cancer 3 94.12 Adenocarcinoma 3 88.00 Malaria 38 79.88 Hyperalgesia 4 75.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The role of SPINK1 mutations in modifying the expression of PRSS1 mutations is unclear but appears to be of clinical importance.

Gene_expression (expression) of PRSS1

1) Confidence 0.76 Published 2004 Journal Gastroenterol. Clin. North Am. Section Abstract Doc Link 15528017 Disease Relevance 0.78 Pain Relevance 0.12

Using an in-vitro system to observe the biological effect of expression of mutated trypsinogen, we observed that R122H trypsinogen leads to cell death by enhanced intracellular trypsin activity [13].

Gene_expression (expression) of trypsinogen associated with death

2) Confidence 0.63 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 1.11 Pain Relevance 0.12

Therefore, the development of mice expressing higher levels of mutated trypsinogen may offer the opportunity to replicate the human disease.

Gene_expression (expressing) of trypsinogen associated with disease

3) Confidence 0.63 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 1.01 Pain Relevance 0.10

To detect the R122H trypsinogen at the protein level, zymogen granules were separated by isoelectric focussing.

Gene_expression (detect) of R122H trypsinogen (R122H)

4) Confidence 0.63 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.78 Pain Relevance 0.17

The R122H mutation is the most common PRSS1 mutation observed, and patients with the R122H mutation present earlier.

Gene_expression (present) of PRSS1

5) Confidence 0.57 Published 2004 Journal Gastroenterol. Clin. North Am. Section Abstract Doc Link 15528017 Disease Relevance 1.04 Pain Relevance 0.18

TheR122H mutation is the most common PRSS1 mutation observed, and patients with the R122H mutation present earlier.

Gene_expression (present) of PRSS1

6) Confidence 0.56 Published 2005 Journal Clin. Lab. Med. Section Abstract Doc Link 15749231 Disease Relevance 1.04 Pain Relevance 0.18

To date such a construct was not available and this encouraged us to generate a transgenic mouse expressing R122H human cationic trypsinogen.

Gene_expression (expressing) of trypsinogen associated with targeted disruption

7) Confidence 0.55 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.99 Pain Relevance 0.22

This finding indicates that the expression of the R122H cationic trypsinogen gene could slightly aggravate the disease under these conditions.

Gene_expression (expression) of trypsinogen associated with disease

8) Confidence 0.55 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 1.28 Pain Relevance 0.14

In a recent study we showed a higher rate of apoptosis after expression of R122H trypsinogen in the cell line AR4-2J [13].

Gene_expression (expression) of R122H trypsinogen (R122H) associated with apoptosis

9) Confidence 0.49 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.79 Pain Relevance 0.08

We speculate that higher amounts of R122H cationic trypsinogen probably provoke a spontaneous phenotype in mouse.

Gene_expression (amounts) of trypsinogen

10) Confidence 0.47 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.97 Pain Relevance 0.11

Characterisation of a transgenic mouse expressing R122H human cationic trypsinogen Background

Gene_expression (expressing) of trypsinogen associated with targeted disruption

11) Confidence 0.42 Published 2006 Journal BMC Gastroenterol Section Title Doc Link PMC1637108 Disease Relevance 0.66 Pain Relevance 0.04

Analogical, our paper will probably open the discussion on the effect of mutated trypsinogen in pancreatic acinar cells since there are to our knowledge several other groups also developing transgenic animals which express mutated trypsinogen.

Gene_expression (express) of trypsinogen in acinar cells associated with targeted disruption

12) Confidence 0.42 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.86 Pain Relevance 0

The R122H mutation of the cationic trypsinogen was found in patients with hereditary pancreatitis.

Gene_expression (found) of trypsinogen associated with pancreatitis

13) Confidence 0.42 Published 2006 Journal BMC Gastroenterol Section Abstract Doc Link PMC1637108 Disease Relevance 0.51 Pain Relevance 0.03

In summary, we generated transgenic mice expressing low amounts of R122H mutated human cationic trypsinogen.

Gene_expression (expressing) of trypsinogen associated with targeted disruption

14) Confidence 0.42 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.88 Pain Relevance 0

Future attempts to create such a model should focus on a vector construction that may ensure a higher expression rate of the cationic trypsinogen in the pancreata of mice.

Gene_expression (expression) of trypsinogen

15) Confidence 0.42 Published 2006 Journal BMC Gastroenterol Section Body Doc Link PMC1637108 Disease Relevance 0.58 Pain Relevance 0.04

Trypsin 1 is also expressed in S females until 5 days post eclosion, but not at the high levels exhibited by Trypsin 4 [87].

Neg (not) Gene_expression (expressed) of Trypsin 1

16) Confidence 0.01 Published 2006 Journal BMC Genomics Section Body Doc Link PMC1508153 Disease Relevance 0 Pain Relevance 0

AS 113 and AS 408, two unknown gene products; AS 13, a peritrophin-like protein; AS 18, Trypsin 1; and AS 99, Chymotrypsin 2, are significantly less abundantly expressed in the mosquito abdomen at 30 h PBM than in S females and not affected further by ookinete invasion. qRT-PCR (Figure 3E, see below) verifies this expression pattern for Chymotrypsin 2.

Neg (not) Gene_expression (expressed) of Trypsin 1 in abdomen

17) Confidence 0.01 Published 2006 Journal BMC Genomics Section Body Doc Link PMC1508153 Disease Relevance 0.08 Pain Relevance 0

The zymogens trypsinogen IV and pro-p23 were expressed in Escherichia coli and purified to apparent homogeneity.

Gene_expression (expressed) of trypsinogen IV

18) Confidence 0.01 Published 2007 Journal J. Biol. Chem. Section Abstract Doc Link 17623652 Disease Relevance 0.15 Pain Relevance 0.11

General Comments

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